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Thursday, December 20, 2018

Where No Hand Has Gone Before: Probing Mechanobiology at the Cellular Level

Carlos Matellan and Armando E. del Río Hernández

Physical forces and other mechanical stimuli are fundamental regulators of cell behavior and function. Cells are also biomechanically competent: they generate forces to migrate, contract, remodel, and sense their environment. As the knowledge of the mechanisms of mechanobiology increases, the need to resolve and probe increasingly small scales calls for novel technologies to mechanically manipulate cells, examine forces exerted by cells, and characterize cellular biomechanics. Here, we review novel methods to quantify cellular force generation, measure cell mechanical properties, and exert localized piconewton and nanonewton forces on cells, receptors, and proteins. The combination of these technologies will provide further insight on the effect of mechanical stimuli on cells and the mechanisms that convert these stimuli into biochemical and biomechanical activity.

DOI

The Complex Conformational Dynamics of Neuronal Calcium Sensor-1: A Single Molecule Perspective

Dhawal Choudhary, Birthe B. Kragelund, Pétur O. Heidarsson and Ciro Cecconi

The human neuronal calcium sensor-1 (NCS-1) is a multispecific two-domain EF-hand protein expressed predominantly in neurons and is a member of the NCS protein family. Structure-function relationships of NCS-1 have been extensively studied showing that conformational dynamics linked to diverse ion-binding is important to its function. NCS-1 transduces Ca2+ changes in neurons and is linked to a wide range of neuronal functions such as regulation of neurotransmitter release, voltage-gated Ca2+ channels and neuronal outgrowth. Defective NCS-1 can be deleterious to cells and has been linked to serious neuronal disorders like autism. Here, we review recent studies describing at the single molecule level the structural and mechanistic details of the folding and misfolding processes of the non-myristoylated NCS-1. By manipulating one molecule at a time with optical tweezers, the conformational equilibria of the Ca2+-bound, Mg2+-bound and apo states of NCS-1 were investigated revealing a complex folding mechanism underlain by a rugged and multidimensional energy landscape. The molecular rearrangements that NCS-1 undergoes to transit from one conformation to another and the energetics of these reactions are tightly regulated by the binding of divalent ions (Ca2+ and Mg2+) to its EF-hands. At pathologically high Ca2+ concentrations the protein sometimes follows non-productive misfolding pathways leading to kinetically trapped and potentially harmful misfolded conformations. We discuss the significance of these misfolding events as well as the role of inter-domain interactions in shaping the energy landscape and ultimately the biological function of NCS-1. The conformational equilibria of NCS-1 are also compared to those of calmodulin (CaM) and differences and similarities in the behavior of these proteins are rationalized in terms of structural properties.

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High-performance reconstruction of microscopic force fields from Brownian trajectories

Laura Pérez García, Jaime Donlucas Pérez, Giorgio Volpe, Alejandro V. Arzola & Giovanni Volpe

The accurate measurement of microscopic force fields is crucial in many branches of science and technology, from biophotonics and mechanobiology to microscopy and optomechanics. These forces are often probed by analysing their influence on the motion of Brownian particles. Here we introduce a powerful algorithm for microscopic force reconstruction via maximum-likelihood-estimator analysis (FORMA) to retrieve the force field acting on a Brownian particle from the analysis of its displacements. FORMA estimates accurately the conservative and non-conservative components of the force field with important advantages over established techniques, being parameter-free, requiring ten-fold less data and executing orders-of-magnitude faster. We demonstrate FORMA performance using optical tweezers, showing how, outperforming other available techniques, it can identify and characterise stable and unstable equilibrium points in generic force fields. Thanks to its high performance, FORMA can accelerate the development of microscopic and nanoscopic force transducers for physics, biology and engineering.

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Approximate and explicit expression of optical forces and pull-in instability of a silicon nano-optomechanical device

K. F. Wang and Baolin Wang

Nano-optomechanical systems actuated by optical forces enable many interesting scientific and technological applications. They are vulnerable to the effects of surface stress and Casimir forces. Therefore, calculation of optical forces is essential for the reliability applications of these advanced devices. In this paper, an approximate and explicit expression is developed for the evaluation of the optical force existing between a waveguide and a substrate through the effective refractive index. The influences of surface stress and Casimir forces on the pull-in instability of a silicon nano-optomechanical device actuated by optical forces are investigated. It is found that if neglecting the effect of surface stress, the maximum size, which indicates the device can be safely fabricated, will be over-predicted. The surface stress reduces the critical optical power and its effect is more significant for a slender waveguide.

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Nonequilibrium Energetics of Molecular Motor Kinesin

Takayuki Ariga, Michio Tomishige, and Daisuke Mizuno

Nonequilibrium energetics of single molecule translational motor kinesin was investigated by measuring heat dissipation from the violation of the fluctuation-response relation of a probe attached to the motor using optical tweezers. The sum of the dissipation and work did not amount to the input free energy change, indicating large hidden dissipation exists. Possible sources of the hidden dissipation were explored by analyzing the Langevin dynamics of the probe, which incorporates the two-state Markov stepper as a kinesin model. We conclude that internal dissipation is dominant.

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Rapid discrimination of colon cancer cells with single base mutation in KRAS gene segment using laser tweezers Raman spectroscopy

Mengmeng Liu, Xiujie Liu, Zufang Huang, Xiaoqiong Tang, Xueliang Lin, Yunchao Xu, Guannan Chen, Hang Fai Kwok, Yao Lin, Shangyuan Feng

Laser tweezers Raman spectroscopy (LTRS) as a label‐free and non‐invasive technology has been proven to be an ideal tool for analysis of single living cells which provides important fingerprint information without interference from surrounding environments. For the first time, LTRS system was successfully employed to examine the colon cancer cells with single base mutation in KRAS gene segment including DKS‐8 (KRAS wild‐type) and DLD‐1 (KRAS mutant‐type), HKE‐3 (KRAS wild‐type) and HCT‐116 (KRAS mutant‐type). Spectra changes of some vital biomolecules due to the gene mutation state were sensitively recorded by our home‐made LTRS system. As a result of the comparison between DKS‐8 and DLD‐1 cells, an index of 97.5% of correct classification was obtained by combining LTRS with PCA‐LDA statistical analysis, while an index of 97.0% of correct classification was achieved between HKE‐3 and HCT‐116 cells. Moreover, between wild‐type cells (DKS‐8 and HKE‐3) versus mutant‐type cells (DLD‐1 and HCT‐116), the index of correct classification was 81.2%, which was quite encouraging. Our preliminary results showed that the LTRS system coupled with PCA‐LDA analysis will have a great potential for further applications in the rapid and label‐free detection of circulating tumor cells in liquid biopsy.

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Soft Hyaluronic Gels Promote Cell Spreading, Stress Fibers, Focal Adhesion, and Membrane Tension by Phosphoinositide Signaling, Not Traction Force

Kalpana Mandal, Dikla Raz-Ben Aroush, Zachary Tobias Graber, Bin Wu, Chan Young Park, Jeffery J. Fredberg, Wei Guo, Tobias Baumgart, and Paul A. Janmey

Cells respond to both physical and chemical aspects of their substrate. Whether intracellular signals initiated by physical stimuli are fundamentally different from those elicited by chemical stimuli is an open question. Here, we show that the requirement for a stiff substrate (and, therefore, high cellular tension) for cells to produce large focal adhesions and stress fibers is obviated when a soft substrate contains both hyaluronic acid (HA) and an integrin ligand (collagen I). HA is a major extracellular matrix component that is often up-regulated during wound healing and tumor growth. HA, together with collagen I, promotes hepatocellular carcinoma cell (Huh7) spreading on very soft substrates (300 Pa), resulting in morphology and motility similar to what these cells develop only on stiff substrates (>30 kPa) formed by polyacrylamide that contains collagen but not HA. The effect of HA requires turnover of polyphosphoinositides and leads to the activation of Akt. The inhibition of polyphosphoinositide turnover causes Huh7 cells and fibroblasts to decrease spreading and detach, whereas cells on stiffer substrates show almost no response. Traction force microscopy shows that the cell maintains a low strain energy and net contractile moment on HA substrates compared to stiff polyacrylamide substrates. Membrane tension measured by tether pulling is similar on soft HA and stiff polyacrylamide substrates. These results suggest that simultaneous signaling stimulated by HA and an integrin ligand can generate phosphoinositide-mediated signals to the cytoskeleton that reproduce those generated by high cellular tension.

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Wednesday, December 19, 2018

Optical Rotational Self-Assembly at Air-Water Surface by a Single Vortex Beam

Xintong Chen, Weizhu Cheng, Mingyuan Xie, Fuli Zhao

Self-assembly and relevant quantitative measurements of 4um polystyrene microspheres at air-water surface were realized by utilizing optical tweezers with a low-numerical-aperture (NA) and long-working-distance (WD) microscope objective. It showed that the rotation velocity of a single microsphere varies with a nearly linear dependence on incident laser power with the existence of surface tension at air-water interface. The self-assembly experiments show that the rotation velocity of the bridging particle chain increases clearly as the particle number increases. This work would contribute to the related researches of micro granular structure fabrication and bio-printing of cell tissues.

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Using optical tweezers to construct an upconversion luminescent resonance energy transfer analytical platform

Cheng-Yu Li, Ya-Feng Kang, Bei Zheng, Chun-Miao Xu, Chong-Yang Song, Dai-Wen Pang, Hong-Wu Tang

We report a new upconversion nanoparticles (UCNPs) based luminescent resonance energy transfer (LRET) analytical platform by making use of optical tweezers technology. The LRET model is designed by simultaneously conjugating Yb3+ and Er3+ co-doped UCNPs (as the donors) and tetramethyl rhodamine (TAMRA) molecules (as the acceptors) on microspheres to fabricate complex microspheres. Upon a single complex microsphere entering the three-dimensional potential well formed with a tightly focused 980 nm Guassian-shaped laser beam, it is optically trapped and concurrently the upconversion emission is excited, whereby the donor signals are transferred to the acceptors. As a proof-of-concept investigation, microRNA-21 sequences are selected as the targets, by which the distance between the two perfectly matched luminophors is controlled to several nanometers via nucleic acid hybridization. Without the involvement of luminescence amplification strategies, the proposed single microsphere based LRET method shows highly competitive sensitivity with a limit of detection down to 114 fM and satisfactory specificity towards microRNAs detection. Moreover, its practical working ability is demonstrated by credibly quantifying the absolute contents of miRNA-21 sequences in three cancer cell lines and even tracing the targets in as few as 100 cancer cells. Thus, this favorable analytical methodology provides an alternative for bioassays and holds certain potential in biomedical applications.

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Binding of a Telomestatin Derivative Changes Mechanical Anisotropy of Human Telomeric G‐Quadruplex

Sagun Jonchhe, Chiran Ghimire, Yunxi Cui, Shogo Sasaki, Mason McCool, Soyoung Park, Keisuke Iida, Prof. Kazuo Nagasawa, Prof. Hiroshi Sugiyama, Prof. Hanbin Mao

Mechanical anisotropy is an essential property for biomolecules to assume structural and functional roles in mechanobiology. However, there is insufficient information on the mechanical anisotropy of ligand–biomolecule complexes. Herein, we investigated the mechanical property of individual human telomeric G‐quadruplexes bound to telomestatin, using optical tweezers. Stacking of the ligand to the G‐tetrad planes changes the conformation of the G‐quadruplex, which resembles a balloon squeezed in certain directions. Such a squeezed balloon effect strengthens the G‐tetrad planes, but dislocates and weakens the loops in the G‐quadruplex upon ligand binding. These dynamic interactions indicate that the binding between the ligand and G‐quadruplex follows the induced‐fit model. We anticipate that the altered mechanical anisotropy of the ligand–G‐quadruplex complex can add additional level of regulations on the motor enzymes that process DNA or RNA molecules.

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Random Formation of G-Quadruplexes in the Full-Length Human Telomere Overhangs Leads to a Kinetic Folding Pattern with Targetable Vacant G-Tracts

Jibin Abraham Punnoose, Yue Ma, Mohammed Enamul Hoque, Yunxi Cui, Shogo Sasaki, Athena Huixin Guo, Kazuo Nagasawa, and Hanbin Mao

G-Quadruplexes formed in the 3′ telomere overhang (∼200 nucleotides) have been shown to regulate biological functions of human telomeres. The mechanism governing the population pattern of multiple telomeric G-quadruplexes is yet to be elucidated inside the telomeric overhang in a time window shorter than thermodynamic equilibrium. Using a single-molecule force ramping assay, we quantified G-quadruplex populations in telomere overhangs over a full physiological range of 99–291 nucleotides. We found that G-quadruplexes randomly form in these overhangs within seconds, which leads to a population governed by a kinetic, rather than a thermodynamic, folding pattern. The kinetic folding gives rise to vacant G-tracts between G-quadruplexes. By targeting these vacant G-tracts using complementary DNA fragments, we demonstrated that binding to the telomeric G-quadruplexes becomes more efficient and specific for telomestatin derivatives.

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Tuesday, December 18, 2018

Repulsive/attractive interaction among compact DNA molecules as judged through laser trapping: difference between linear- and branched-chain polyamines

Yusuke Kashiwagi, Takashi Nishio, Masatoshi Ichikawa, Chwen-Yang Shew, Naoki Umezawa, Tsunehiko Higuchi, Koichiro Sadakane, Yuko Yoshikawa, Kenichi Yoshikawa

It is well known that polyamines induce a folding transition from an elongated coil to a compact globule state for giant DNA larger than several tens of kbp (kilo base pairs). Here, we studied the interaction between compact DNA molecules in the presence of linear and branched-chain isomers of polyamines. We compared the stability of the assembly among plural number of compact DNA molecules generated by laser trapping. As a result, the assembly of compact DNAs with a linear-chain polyamine is stable even after the laser is switched off. On the other hand, the assembly of DNAs with a branched-chain polyamine disperses into individual compact DNAs when the laser is switched off. Thus, compact DNAs with linear- and branched-chain polyamines attract and repel each other, respectively. This difference in the effects of linear and branched polyamines is discussed in terms of the steric interaction between negatively charged double-strand DNA and cationic polyamines.

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Optimized rotation of an optically trapped particle for micro mixing

Mahmoud Hosseinzadeh, Faegheh Hajizadeh, Mehdi Habibi, Hossain Milani Moghaddam, and S. Nader S. Reihani
The angular momentum transferred by circularly polarized photons is able to rotate an optically trapped microparticle. Here, the optically rotating particle is introduced as an active micromixer to reduce the mixing time in a microfluidic system. To optimize the system for microfluidic application, the effect of several optical parameters such as spherical aberration and the numerical aperture of the objective on the rotation rate of a trapped particle is investigated. The results show that the optimized depth for the rotation of a particle is located close to the coverslip and can be changed by a fine adjustment of the refractive index of the immersion oil. By applying the obtained optimized optical parameters on a trapped particle at the interface of two fluids in a microchannel, the mixing length is reduced by a factor of ∼2.

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High-performance solar-blind SnO2 nanowire photodetectors assembled using optical tweezers

Jianwei Yan, Yang Chen, Xiaowu Wang, Ying Fu, Juxiang Wang, Jia Sun, Guozhang Dai, Shaohua Tao and Yongli Gao

One-dimensional semiconducting SnO2 nanowires with wide bandgaps are promising candidates to build many important optoelectronic devices. Because building these devices involves the assembly of nanowires into complex structures, manipulation of the active materials needs to be done with high spatial precision. In this paper, an optical tweezer system, comprising a spatial light-modulator, a microscope, and optical elements, is used to individually trap, transfer, and assemble SnO2 nanowires into two-terminal photodetectors in a liquid environment. After the assembly using optical trapping, the two ends of the SnO2 nanowire photodetectors, which are connected with the electrodes, were further stabilized using a focused laser. During exposure to 275 nm deep-ultraviolet light, the as-assembled photodetectors show a high Iph/Idark ratio of 2.99 × 105, a large responsivity of 4.3 × 104 A W−1, an excellent external quantum efficiency of 1.94 × 105, and a high detectivity of 2.32 × 1013 Jones. The photoresponse-speed of the devices could be improved further using passivation with a polymer. The rise and decay times are about 60 ms and 100 ms, respectively. As a result of this study, we can confirm that non-contact optical trapping can enable the construction of nanowire architectures for optoelectronic, bioelectronic, and other devices.

Optical Tweezers: A Force to Be Reckoned With

Jessica L.Killian, Fan Ye, Michelle D.Wang
The 2018 Nobel Prize in Physics has been awarded jointly to Arthur Ashkin for the discovery and development of optical tweezers and their applications to biological systems and to Gérard Mourou and Donna Strickland for the invention of laser chirped pulse amplification. Here we focus on Arthur Ashkin and how his revolutionary work opened a window into the world of molecular mechanics and spurred the rise of single-molecule biophysics.

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Opto-Thermophoretic Attraction, Trapping, and Dynamic Manipulation of Lipid Vesicles

Eric H. Hill, Jingang Li, Linhan Lin, Yaoran Liu, and Yuebing Zheng

Lipid vesicles are important biological assemblies, which are critical to biological transport processes, and vesicles prepared in the lab are a workhorse for studies of drug delivery, protein unfolding, biomolecular interactions, compartmentalized chemistry, and stimuli-responsive sensing. The current method of using optical tweezers for holding lipid vesicles in place for single-vesicle studies suffers from limitations such as high optical power, rigorous optics, and small difference in the refractive indices of vesicles and water. Herein, we report the use of plasmonic heating to trap vesicles in a temperature gradient, allowing long-range attraction, parallel trapping, and dynamic manipulation. The capabilities and limitations with respect to thermal effects on vesicle structure and optical spectroscopy are discussed. This simple approach allows vesicle manipulation using down to 3 orders of magnitude lower optical power and at least an order of magnitude higher trapping stiffness per unit power than traditional optical tweezers while using a simple optical setup. In addition to the benefit provided by the relaxation of these technical constraints, this technique can complement optical tweezers to allow detailed studies on thermophoresis of optically trapped vesicles and effects of locally generated thermal gradients on the physical properties of lipid vesicles. Finally, the technique itself and the large-scale collection of vesicles have huge potential for future studies of vesicles relevant to detection of exosomes, lipid-raft formation, and other areas relevant to the life sciences.

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Friday, December 14, 2018

Biomechanical Characterization at the Cell Scale: Present and Prospects

Francesco Basoli, Sara Maria Giannitelli, Manuele Gori, Pamela Mozetic, Alessandra Bonfanti, Marcella Trombetta and Alberto Rainer

The rapidly growing field of mechanobiology demands for robust and reproducible characterization of cell mechanical properties. Recent achievements in understanding the mechanical regulation of cell fate largely rely on technological platforms capable of probing the mechanical response of living cells and their physico–chemical interaction with the microenvironment. Besides the established family of atomic force microscopy (AFM) based methods, other approaches include optical, magnetic, and acoustic tweezers, as well as sensing substrates that take advantage of biomaterials chemistry and microfabrication techniques. In this review, we introduce the available methods with an emphasis on the most recent advances, and we discuss the challenges associated with their implementation.

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A vector holographic optical trap

Nkosiphile Bhebhe, Peter A. C. Williams, Carmelo Rosales-Guzmán, Valeria Rodriguez-Fajardo & Andrew Forbes

The invention of optical tweezers almost forty years ago has triggered applications spanning multiple disciplines and has also found its way into commercial products. A major breakthrough came with the invention of holographic optical tweezers (HOTs), allowing simultaneous manipulation of many particles, traditionally done with arrays of scalar beams. Here we demonstrate a vector HOT with arrays of digitally controlled Higher-Order Poincaré Sphere (HOPS) beams. We employ a simple set-up using a spatial light modulator and show that each beam in the array can be manipulated independently and set to an arbitrary HOPS state, including replicating traditional scalar beam HOTs. We demonstrate trapping and tweezing with customized arrays of HOPS beams comprising scalar orbital angular momentum and cylindrical vector beams, including radially and azimuthally polarized beams simultaneously in the same trap. Our approach is general enough to be easily extended to arbitrary vector beams, could be implemented with fast refresh rates and will be of interest to the structured light and optical manipulation communities alike.

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Asymmetric Ionic Conditions Generate Large Membrane Curvatures

Marzieh Karimi, Jan Steinkühler, Debjit Roy, Raktim Dasgupta, Reinhard Lipowsky, and Rumiana Dimova

Biological membranes possess intrinsic asymmetry. This asymmetry is associated not only with leaflet composition in terms of membrane species but also with differences in the cytosolic and periplasmic solutions containing macromolecules and ions. There has been a long quest for understanding the effect of ions on the physical and morphological properties of membranes. Here, we elucidate the changes in the mechanical properties of membranes exposed to asymmetric buffer conditions and the associated curvature generation. As a model system, we used giant unilamellar vesicles (GUVs) with asymmetric salt and sugar solutions on the two sides of the membrane. We aspirated the GUVs into micropipettes and attached small beads to their membranes. An optical tweezer was used to exert a local force on a bead, thereby pulling out a membrane tube from the vesicle. The assay allowed us to measure the spontaneous curvature and the bending rigidity of the bilayer in the presence of different ions and sugar. At low sugar/salt (inside/out) concentrations, the membrane spontaneous curvature generated by NaCl and KCl is close to zero, but negative in the presence of LiCl. In the latter case, the membrane bulges away from the salt solution. At high sugar/salt conditions, the membranes were observed to become more flexible and the spontaneous curvature was enhanced to even more negative values, comparable to those generated by some proteins. Our findings reveal the reshaping role of alkali chlorides on biomembranes.

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Numeric corrections to the proximity-force approximation for lateral Casimir forces

Fanglin Bao and Kezhang Shi

We report a numeric investigation on the proximity-force approximation (PFA) for lateral Casimir forces between a sphere and a grating. Near-unity force correlations are found between the approximated force and the exact values, due to geometric effects. A minimal model yields a best-fit expression of the numeric correction to the PFA, for gratings in the dilute limit. Our results are not restricted to specific material of the sphere, and allows simple estimation of Casimir interactions for micro-scale spheres, and thus shall be useful in relevant experimental and engineering Casimir applications.

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Optical and Thermophoretic Control of Janus Nanopen Injection into Living Cells

Christoph M. Maier, Maria Ana Huergo, Sara Milosevic, Carla Pernpeintner, Miao Li, Dhruv P. Singh, Debora Walker, Peer Fischer, Jochen Feldmann, and Theobald Lohmüller

Devising strategies for the controlled injection of functional nanoparticles and reagents into living cells paves the way for novel applications in nanosurgery, sensing, and drug delivery. Here, we demonstrate the light-controlled guiding and injection of plasmonic Janus nanopens into living cells. The pens are made of a gold nanoparticle attached to a dielectric alumina shaft. Balancing optical and thermophoretic forces in an optical tweezer allows single Janus nanopens to be trapped and positioned on the surface of living cells. While the optical injection process involves strong heating of the plasmonic side, the temperature of the alumina stays significantly lower, thus allowing the functionalization with fluorescently labeled, single-stranded DNA and, hence, the spatially controlled injection of genetic material with an untethered nanocarrier.

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Size-dependent trapping behavior and optical emission study of NaYF4 nanorods in optical fiber tip tweezers

G. Leménager, M. Thiriet, F. Pourcin, K. Lahlil, F. Valdivia-Valero, G. Colas des Francs, T. Gacoin, and J. Fick

Trapping of NaYF4:Er/Yb/Gd nanorods using an original optical fiber-tip tweezers is reported. Depending on their length, nanorods are reproducibly trapped in single or dual fiber tip configurations. Short rods of 600 nm length are trapped with two fiber tips facing each other. In contrary, long rods (1.9 μm) can be stably trapped at the apex of one single fiber tip and at a second stable trapping position 5 μm away from the tip. The up-conversion emission of trapped long nanorods is studied as a function of the position on the nanorod and in three orthogonal directions. The experimental results are discussed using numerical simulations based on exact Maxwell Stress Tensor approach.

DOI

Wednesday, December 12, 2018

Reynolds number and diffusion coefficient of micro- and nano-aerosols in optical pipelines

Amin Mousavi, Fahimeh Hosseinibalam, Smaeyl Hassanzadeh

In this study, the microscopic particle motion inside an optical pipeline, such as particle motion through a mechanical tube, is investigated. The photons in an optical tube guide the particles towards the center of the light beam by inducing photophoretic and radiation pressure forces. Laguerre–Gaussian- and Bessel-like beams are examples of such optical tubes. The Reynolds number of particle motion in optical tubes is investigated. The power of the light beam and the ratio of the particle radius to the light beam ring radius influence the turbulence of the particle flow and the value of the Reynolds number. The diffusion coefficient of particle movement in such pipelines is derived, which indicates that an optical tube is a good tool for guiding and trapping particles in micron- and nanometer-scale dimensions.

Crossover from positive to negative optical torque in mesoscale optical matter

Fei Han, John A. Parker, Yuval Yifat, Curtis Peterson, Stephen K. Gray, Norbert F. Scherer & Zijie Yan

The photons in circularly polarized light can transfer their quantized spin angular momentum to micro- and nanostructures via absorption and scattering. This normally exerts positive torque on the objects wher the sign (i.e., handedness or angular direction) follows that of the spin angular momentum. Here we show that the sign of the optical torque can be negative in mesoscopic optical matter arrays of metal nanoparticles (NPs) assembled in circularly polarized optical traps. Crossover from positive to negative optical torque, which occurs for arrays with different number, separation and configuration of the constituent particles, is shown to result from many-body interactions as clarified by electrodynamics simulations. Our results establish that both positive and negative optical torque can be readily realized and controlled in optical matter arrays. This property and reconfigurability of the arrays makes possible programmable materials for optomechanical, microrheological and biological applications.

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Optical Trapping, Optical Binding, and Rotational Dynamics of Silicon Nanowires in Counter-Propagating Beams

Maria G. Donato, Oto Brzobohatý, Stephen H. Simpson, Alessia Irrera, Antonio A. Leonardi, Maria J. Lo Faro, Vojtěch Svak, Onofrio M. Maragò, and Pavel Zemánek

Silicon nanowires are held and manipulated in controlled optical traps based on counter-propagating beams focused by low numerical aperture lenses. The double-beam configuration compensates light scattering forces enabling an in-depth investigation of the rich dynamics of trapped nanowires that are prone to both optical and hydrodynamic interactions. Several polarization configurations are used, allowing the observation of optical binding with different stable structure as well as the transfer of spin and orbital momentum of light to the trapped silicon nanowires. Accurate modeling based on Brownian dynamics simulations with appropriate optical and hydrodynamic coupling confirms that this rich scenario is crucially dependent on the non-spherical shape of the nanowires. Such an increased level of optical control of multiparticle structure and dynamics open perspectives for nanofluidics and multi-component light-driven nanomachines.
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A three-dimensional steerable optical tweezer system for ultracold atoms

C. S. Chisholm, R. Thomas, A. B. Deb, and N. Kjærgaard

We present a three-dimensional steerable optical tweezer system based on two pairs of acousto-optic deflectors. Radio frequency signals used to steer the optical tweezers are generated by direct digital synthesis, and multiple time averaged cross beam dipole traps can be produced through rapid frequency toggling. We produce arrays of ultracold atomic clouds in both horizontal and vertical planes and use this to demonstrate the three-dimensional nature of this optical tweezer system.

DOI

Effect of spectrin network elasticity on the shapes of erythrocyte doublets

Masoud Hoore, François Yaya, Thomas Podgorski, Christian Wagner, Gerhard Gompper and Dmitry A. Fedosov
Red blood cell (RBC) aggregates play an important role in determining blood rheology. RBCs in plasma or polymer solution interact attractively to form various shapes of RBC doublets, where the attractive interactions can be varied by changing the solution conditions. A systematic numerical study on RBC doublet formation is performed, which takes into account the shear elasticity of the RBC membrane due to the spectrin cytoskeleton, in addition to the membrane bending rigidity. RBC membranes are modeled by two-dimensional triangular networks of linked vertices, which represent three-dimensional cell shapes. The phase space of RBC doublet shapes in a wide range of adhesion strengths, reduced volumes, and shear elasticities is obtained. The shear elasticity of the RBC membrane changes the doublet phases significantly. Experimental images of RBC doublets in different solutions show similar configurations. Furthermore, we show that rouleau formation is affected by the doublet structure.

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Nanoscale virtual potentials using optical tweezers

Avinash Kumar and John Bechhoefer

We combine optical tweezers with feedback to impose arbitrary potentials on a colloidal particle. The feedback trap detects a particle's position, calculates a force based on an imposed “virtual potential,” and shifts the trap center to generate the desired force. We create virtual harmonic and double-well potentials to manipulate particles. The harmonic potentials can be chosen to be either weaker or stiffer than the underlying optical trap. Using this flexibility, we create an isotropic trap in three dimensions. Finally, we show that we can create a virtual double-well potential with fixed well separation and adjustable barrier height. These are accomplished at length scales down to 11 nm, a feat that is difficult or impossible to create with standard optical-tweezer techniques such as time sharing, dual beams, or spatial light modulators.

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Monday, December 10, 2018

Optimizing optical tweezing with directional scattering in composite microspheres

R. Ali, F. A. Pinheiro, F. S. S. Rosa, R. S. Dutra, and P. A. Maia Neto

We demonstrate that achieving zero backward scattering (ZBS), i.e., the first Kerker condition, allows for optical tweezing of high-index microspheres, which cannot be trapped using standard techniques. For this purpose, we propose an alternative material platform based on composite metamaterials. By tuning the volume filling fraction of inclusions and the microsphere radius, stable trapping can be achieved provided that ZBS is combined with the condition for destructive interference between the fields reflected at the external and internal interfaces of the microsphere when located at the focal point. By using the Mie-Debye-spherical aberration theory, we also show that the ZBS condition is even more useful in realistic, standard optical tweezer setups, in which spherical aberration is unavoidable due to refraction at the interface between the glass slide and the water-filled sample. Altogether, our findings not only pave the way for possible new trapping designs and applications but also unveil the role of backscattering in the physics of optical tweezers.

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Theory of optical forces on small particles by multiple plane waves

Ehsan Mobini, Aso Rahimzadegan, Carsten Rockstuhl, and Rasoul Alaee

We theoretically investigate the optical force exerted on an isotropic particle illuminated by a superposition of plane waves. We derive explicit analytical expressions for the exerted force up to quadrupolar polarizabilities. Based on these analytical expressions, we demonstrate that an illumination consisting of two tilted plane waves can provide a full control on the optical force. In particular, optical pulling, pushing, and lateral forces can be obtained by the proper tuning of illumination parameters. Our findings might unlock multiple applications based on a deterministic control of the spatial motion of small particles.

Optical Trapping and Manipulation of Superparamagnetic Beads Using Annular-Shaped Beams

Leandro Oliveira, Warlley H. Campos and Marcio S. Rocha

We propose an optical tweezers setup based on an annular-shaped laser beam that is efficient to trap 2.8 μ m-diameter superparamagnetic particles. The optical trapping of such particles was fully characterized, and a direct absolute comparison with a geometrical optics model was performed. With this comparison, we were able to show that light absorption by the superparamagnetic particles is negligible for our annular beam tweezers, differing from the case of conventional Gaussian beam tweezers, in which laser absorption by the beads makes stable trapping difficult. In addition, the trap stiffness of the annular beam tweezers increases with the laser power and with the bead distance from the coverslip surface. While this first result is expected and similar to that achieved for conventional Gaussian tweezers, which use ordinary dielectric beads, the second result is quite surprising and different from the ordinary case, suggesting that spherical aberration is much less important in our annular beam geometry. The results obtained here provide new insights into the development of hybrid optomagnetic tweezers, which can apply simultaneously optical and magnetic forces on the same particles.

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Anisotropic mechanics and dynamics of a living mammalian cytoplasm

Satish Kumar Gupta, Yiwei Li and Ming Guo

During physiological processes, cells can undergo morphological changes that can result in a significant redistribution of the cytoskeleton causing anisotropic behavior. Evidence of anisotropy in cells under mechanical stimuli exists; however, the role of cytoskeletal restructuring resulting from changes in cell shape in mechanical anisotropy and its effects remain unclear. In the present study, we examine the role of cell morphology in inducing anisotropy in both intracellular mechanics and dynamics. We change the aspect ratio of cells by confining the cell width and measuring the mechanical properties of the cytoplasm using optical tweezers in both the longitudinal and transverse directions to quantify the degree of mechanical anisotropy. These active microrheology measurements are then combined with intracellular movement to calculate the intracellular force spectrum using force spectrum microscopy (FSM), from which the degree of anisotropy in dynamics and force can be quantified. We find that unrestricted cells with aspect ratio (AR) ∼1 are isotropic; however, when cells break symmetry, they exhibit significant anisotropy in cytoplasmic mechanics and dynamics.

DOI

Host membrane glycosphingolipids and lipid microdomains facilitate Histoplasma capsulatum internalisation by macrophages

Allan J. Guimarães, Mariana Duarte de Cerqueira, Daniel Zamith‐Miranda, Pablo H. Lopez, Marcio L. Rodrigues, Bruno Pontes, Nathan B. Viana, Carlos M. DeLeon‐Rodriguez, Diego Conrado Pereira Rossi, Arturo Casadevall, Andre M.O. Gomes, Luis R. Martinez, Ronald L. Schnaar, Joshua D. Nosanchuk, Leonardo Nimrichter

Recognition and internalisation of intracellular pathogens by host cells is a multifactorial process, involving both stable and transient interactions. The plasticity of the host cell plasma membrane is fundamental in this infectious process. Here, the participation of macrophage lipid microdomains during adhesion and internalisation of the fungal pathogen Histoplasma capsulatum (Hc) was investigated. An increase in membrane lateral organisation, which is a characteristic of lipid microdomains, was observed during the first steps of Hc–macrophage interaction. Cholesterol enrichment in macrophage membranes around Hc contact regions and reduced levels of Hc–macrophage association after cholesterol removal also suggested the participation of lipid microdomains during Hc–macrophage interaction. Using optical tweezers to study cell‐to‐cell interactions, we showed that cholesterol depletion increased the time required for Hc adhesion. Additionally, fungal internalisation was significantly reduced under these conditions. Moreover, macrophages treated with the ceramide‐glucosyltransferase inhibitor (P4r) and macrophages with altered ganglioside synthesis (from B4galnt1−/− mice) showed a deficient ability to interact with Hc. Coincubation of oligo‐GM1 and treatment with Cholera toxin Subunit B, which recognises the ganglioside GM1, also reduced Hc association. Although purified GM1 did not alter Hc binding, treatment with P4 significantly increased the time required for Hc binding to macrophages. The content of CD18 was displaced from lipid microdomains in B4galnt1−/− macrophages. In addition, macrophages with reduced CD18 expression (CD18low) were associated with Hc at levels similar to wild‐type cells. Finally, CD11b and CD18 colocalised with GM1 during Hc–macrophage interaction. Our results indicate that lipid rafts and particularly complex gangliosides that reside in lipid rafts stabilise Hc–macrophage adhesion and mediate efficient internalisation during histoplasmosis.

DOI

Mechanobiology: protein refolding under force

Ionel Popa, Ronen Berkovich

The application of direct force to a protein enables to probe wide regions of its energy surface through conformational transitions as unfolding, extending, recoiling, collapsing, and refolding. While unfolding under force typically displayed a two-state behavior, refolding under force, from highly extended unfolded states, displayed a more complex behavior. The first recording of protein refolding at a force quench step displayed an initial rapid elastic recoil, followed by a plateau phase at some extension, concluding with a collapse to a final state, at which refolding occurred. These findings stirred a lively discussion, which led to further experimental and theoretical investigation of this behavior. It was demonstrated that the polymeric chain of the unfolded protein is required to fully collapse to a globular conformation for the maturation of native structure. This behavior was modeled using one-dimensional free energy landscape over the end-to-end length reaction coordinate, the collective measured variable. However, at low forces, conformational space is not well captured by such models, and using two-dimensional energy surfaces provides further insight into the dynamics of this process. This work reviews the main concepts of protein refolding under constant force, which is essential for understanding how mechanotransducing proteins operate in vivo.

DOI

Characterizing abrupt transitions in stochastic dynamics

Klaus Lehnertz, Lina Zabawa and M Reza Rahimi Tabar

Data sampled at discrete times appears as a succession of discontinuous jumps, even if the underlying trajectory is continuous. We analytically derive a criterion that allows one to check whether for a given, even noisy time series the underlying process has a continuous (diffusion) trajectory or has jump discontinuities. This enables one to detect and characterize abrupt changes (jump events) in given time series. The proposed criterion is validated numerically using synthetic continuous and discontinuous time series. We demonstrate applicability of our criterion to distinguish diffusive and jumpy behavior by a data-driven inference of higher-order conditional moments from empirical observations.

DOI

Friday, December 7, 2018

Versatile applications of three-dimensional objects fabricated by two-photon-initiated polymerization

Cheol Woo Ha, Prem Prabhakaran, and Kwang-Sup Lee

In this topical review of two-photon stereolithography (TPS), we discuss novel materials and demonstrate applications of this technology. Two-photon-initiated chemical processes are used to fabricate arbitrary three-dimensional structures in TPS. In the first part of this article, the development of novel photoactive materials to fabricate pure inorganic or organic–inorganic hybrid microstructures is discussed. The second part discusses the fabrication of functional microstructures for highly specific applications to demonstrate the importance of TPS in different fields of science.

DOI

A review of complex vector light fields and their applications

Carmelo Rosales-Guzmán, Bienvenu Ndagano and Andrew Forbes

Vector beams, and in particular vector vortex beams, have found many applications in recent times, both as classical fields and as quantum states. While much attention has focused on the creation and detection of scalar optical fields, it is only recently that vector beams have found their place in the modern laboratory. In this review, we outline the fundamental concepts of vector beams, summarise the various approaches to control them in the laboratory, and give a concise overview of the many applications they have spurned.

DOI

Detecting stimulated Raman responses of molecules in plasmonic gap using photon induced forces

Venkata Ananth Tamma, Lindsey M. Beecher, Jennifer S. Shumaker-Parry, and Hemanta Kumar Wickramasinghe

We demonstrate the stimulated Raman nanoscopy of a small number of molecules in a plasmonic gap, excited without resonant electronic enhancement, measured using near-field photon-induced forces, eliminating the need for far-field optical detection. We imaged 30 nm diameter gold nanoparticles functionalized with a self-assembled monolayer (SAM) of 4-nitrobenzenethiol (4-NBT) molecules. The maximum number of molecules detected by the gold-coated nano-probe at the position of maximum field enhancement could be fewer than about 42 molecules. The molecules were imaged by vibrating an Atomic Force Microscope (AFM) cantilever on its second flexural eigenmode enabling the tip to be controlled much closer to the sample, thereby improving the detected signal-to-noise ratio when compared to vibrating the cantilever on its first flexural eigenmode. We also demonstrate the implementation of stimulated Raman nanoscopy measured using photon-induced force with non-collinear pump and stimulating beams which could have applications in polarization dependent Raman nanoscopy and spectroscopy and pump-probe nano-spectroscopy particularly involving infrared beam/s. We also discuss using photon induced forces as a technique to sort and select best performing metal coated tips for further use in tip-enhanced experiments.

DOI

GCforce: Decomposition of optical force into gradient and scattering parts

Hongxia Zheng, Xinning Yu, Wanli Lu, Jack Ng, Zhifang Lin

A MATLAB function GCforce is presented for the calculation of gradient and scattering parts of optical force (OF). The decomposition of OF into the gradient and scattering parts, or, equivalently, the conservative and nonconservative components, is of great importance to the physical understanding of optical micromanipulation. In this paper, we propose a formulation to decompose the OF acting on a spherical particle immersed in an arbitrary monochromatic optical field, based on the generalized Lorenz–Mietheory and the Cartesian multipole expansion approach. The expressions for the gradient and scattering forces are given explicitly in terms of the partial wave expansion coefficients of the optical field shining on the particle and the Mie coefficients of the particle. A MATLAB function GCforce.m is also presented for the calculation. The explicit and rigorous decomposition of the OF into conservative and nonconservative forces sheds light on the understanding of light–matter interaction as well as contributes significantly to the designing of optical fields to achieve various optical micromanipulation.

DOI

Geometric stabilisation of topological defects on micro-helices and grooved rods in nematic liquid crystals

Maryam Nikkhou and Igor Muševič

We demonstrate how the geometric shape of a rod in a nematic liquid crystal can stabilise a large number of oppositely charged topological defects. A rod is of the same shape as a sphere, both having genus g = 0, which means that the sum of all topological charges of defects on a rod has to be −1 according to the Gauss–Bonnet theorem. If the rod is straight, it usually shows only one hyperbolic hedgehog or a Saturn ring defect with negative unit charge. Multiple unit charges can be stabilised either by friction or large length, which screens the pair-interaction of unit charges. Here we show that the curved shape of helical colloids or the grooved surface of a straight rod create energy barriers between neighbouring defects and prevent their annihilation. The experiments also clearly support the Gauss–Bonnet theorem and show that topological defects on helices or grooved rods always appear in an odd number of unit topological charges with a total topological charge of −1.

DOI

Recent advances in microfluidic cell sorting systems

Yigang Shen, Yaxiaer Yalikun, Yo Tanaka

Effective and high-throughput cell sorting are critical technologies in single cell analysis in biology, medicine and clinical applications. Especially for single cell analysis requiring high accuracy, multiple sorting mechanisms are required, and they need to be well organized into a system based on the sorting ability. Therefore, we classify most recent methods of microfluidic cell sorting as precise or large amount sorting methods based on the ability for sorting the number of cells. Precise sorting applies an instantaneous force (e.g. acoustic, electric, optical, and jet force) to displace cells a short distance to isolate them one by one with relatively high accuracy. Large amount methods use a continuous force (e.g. acoustic, electric, magnetic and passive force) to arrange, separate and purify cell populations with relatively high-throughput. By combining precise sorting and large amount sorting methods, it is possible to achieve a high-accuracy sorting system with high-throughput. Therefore, in this review, we summarized merits and demerits of these advanced technologies of sorting (focusing on those devices in the last five years that have features of high-throughput, portability and high efficiency) to suggest some suitable combinations of large amount and precise sorting methods; then we discussed the direction of single cell sorting and the prospects of the combined microchips.

DOI

Thursday, December 6, 2018

Laser Tweezers Raman Spectroscopy to Detect Effects of Chlorine Dioxide on Individual Nosema bombycis Spores

Yu Zhang, Zhenbin Miao, Xuhua Huang, Xiaochun Wang, Junxian Liu, Guiwen Wang

The microsporidium Nosema bombycis (Nb) causes pebrine, a fatal disease in the sericulture. Nb is effectively killed by chlorine dioxide (ClO2), however, the precise killing mechanism remains unclear. We used laser tweezers Raman spectroscopy to monitor the action of ClO2 on individual Nb spores in real time. Raman peaks of ClO2 appeared in Nb spores, corresponding to decreased peaks of trehalose that gradually disappeared. A peak (1658 cm–1) corresponding to the protein α-helix significantly weakened while that (1668 cm–1) corresponding to irregular protein structures was enhanced, and their intensities were negatively correlated in a certain time range and dependent on ClO2 concentration. The intensities of peaks at 782 cm–1 (nucleic acids) and 1004 cm–1 (phenylalanine of protein) did not change evidently even under extremely high ClO2 concentrations. Thus, ClO2 rapidly permeates the Nb spore wall, changing the protein secondary structure to lose biological function and destroy permeability, causing trehalose to leak out. These effects are ClO2 concentration-dependent, but no other obvious changes to biomacromolecules were detected. Single-cell analysis using laser tweezers Raman spectroscopy (LTRS) is an effective method to monitor the action of chemical sporicides on microbes in real time, providing insight into the heterogeneity of cell stress resistance.

DOI

The T Cell Antigen Receptor α Transmembrane Domain Coordinates Triggering through Regulation of Bilayer Immersion and CD3 Subunit Associations

Kristine N.Brazin, Robert J.Mallis, Andras Boeszoermenyi, Yinnian Feng, Akihiro Yoshizawa, Pedro A.Reche, Pavanjeet Kaur, Kevin Bi, Rebecca E.Hussey, Jonathan S.Duke-Cohan, Likai Song, Gerhard Wagner, Haribabu Arthanari, Matthew J.Lang, Ellis L.Reinherz

Initial molecular details of cellular activation following αβT cell antigen receptor (TCR) ligation by peptide-major histocompatibility complexes (pMHC) remain unexplored. We determined the nuclear magnetic resonance (NMR) structure of the TCRα subunit transmembrane (TM) domain revealing a bipartite helix whose segmentation fosters dynamic movement. Positively charged TM residues Arg251 and Lys256 project from opposite faces of the helix, with Lys256 controlling immersion depth. Their modification caused stepwise reduction in TCR associations with CD3ζζ homodimers and CD3εγ plus CD3εδ heterodimers, respectively, leading to an activated transcriptome. Optical tweezers revealed that Arg251 and Lys256 mutations altered αβTCR-pMHC bond lifetimes, while mutations within interacting TCRα connecting peptide and CD3δ CxxC motif juxtamembrane elements selectively attenuated signal transduction. Our findings suggest that mechanical forces applied during pMHC ligation initiate T cell activation via a dissociative mechanism, shifting disposition of those basic sidechains to rearrange TCR complex membrane topology and weaken TCRαβ and CD3 associations.

DOI

Energy, Linear Momentum, and Angular Momentum of Light: What Do We Measure?

Olivier Emile, Janine Emile

The most commonly observed quantity related to light is its power or, equivalently, its energy. It can be either measured with a bolometer, a photodiode, or estimated with the naked eye. Alternatively, people can measure the light impulse or linear momentum. However, linear momentum is characterized by its transfer to matter, and its precise value is, most of the time, of little use. Energy and linear momentum are linked and can be deduced from each other, from a theoretical point of view. Because the linear momentum measurement is more difficult, energy is the most often measured quantity. In every physical process, angular momentum, like energy and linear momentum, is conserved. However, it is independent and cannot be deduced from the energy or the linear momentum. It can only be estimated via its transfer to matter using a torque observation. Nevertheless, experimentally, the torque is found to be proportional to the optical power. This leads to a need for a quantum interpretation of the optical field in terms of photons. Clear experimental evidences and consequences are presented here and debated.

DOI

Laser-driven structural transformations in dextran-graft-PNIPAM copolymer/Au nanoparticles hybrid nanosystem: the role of plasmon heating and attractive optical forces

Oleg A. Yeshchenko, Antonina P. Naumenko, Nataliya V. Kutsevol and Iulia I. Harahuts

Laser induced structural transformations in a dextran grafted-poly(N-isopropylacrylamide) copolymer/Au nanoparticles (D-g-PNIPAM/AuNPs) hybrid nanosystem in water have been observed. The laser induced local plasmonic heating of Au NPs leads to Lower Critical Solution Temperature (LCST) phase transition in D-g-PNIPAM/AuNPs macromolecules accompanied by their shrinking and aggregation. The hysteresis non-reversible character of the structural transformation in D-g-PNIPAM/AuNPs system has been observed at the decrease of laser intensity, i.e. the aggregates remains in solution after the turn-off the laser illumination. This is an essential difference comparing to the case of usual heating–cooling cycles when there is no formation of aggregates and structural transformations are reversible. Such a fundamental difference has been rationalized as the result of action of attractive optical forces arising due to the excitation of surface plasmons in Au NPs. The attractive plasmonic forces facilitate the formation of the aggregates and counteract their destruction. The laser induced structural transformations have been found to be very sensitive to matching conditions of the resonance of the laser light with surface plasmon resonance proving the plasmonic nature of observed phenomena.

DOI

Nanoradiator-Mediated Deterministic Opto-Thermoelectric Manipulation

Yaoran Liu, Linhan Lin, Bharath Bangalore Rajeeva, Jeremy W. Jarrett, Xintong Li, Xiaolei Peng, Pavana Kollipara, Kan Yao, Deji Akinwande, Andrew K. Dunn, and Yuebing Zheng

Optical manipulation of colloidal nanoparticles and molecules is significant in numerous fields. Opto-thermoelectric nanotweezers exploiting multiple coupling among light, heat, and electric fields enables the low-power optical trapping of nanoparticles on a plasmonic substrate. However, the management of light-to-heat conversion for the versatile and precise manipulation of nanoparticles is still elusive. Herein, we explore the opto-thermoelectric trapping at plasmonic antennas that serve as optothermal nanoradiators to achieve the low-power (∼0.08 mW/μm2) and deterministic manipulation of nanoparticles. Specifically, precise optical manipulation of nanoparticles is achieved via optical control of the subwavelength thermal hot spots. We employ a femtosecond laser beam to further improve the heat localization and the precise trapping of single ∼30 nm semiconductor quantum dots at the antennas where the plasmon–exciton coupling can be tuned. With its low-power, precise, and versatile particle control, the opto-thermoelectric manipulation can have applications in photonics, life sciences, and colloidal sciences.

DOI

Wednesday, December 5, 2018

Dynamics of individual molecular shuttles under mechanical force

Teresa Naranjo, Kateryna M. Lemishko, Sara de Lorenzo, Álvaro Somoza, Felix Ritort, Emilio M. Pérez & Borja Ibarra

Molecular shuttles are the basis of some of the most advanced synthetic molecular machines. In these devices a macrocycle threaded onto a linear component shuttles between different portions of the thread in response to external stimuli. Here, we use optical tweezers to measure the mechanics and dynamics of individual molecular shuttles in aqueous conditions. Using DNA as a handle and as a single molecule reporter, we measure thousands of individual shuttling events and determine the force-dependent kinetic rates of the macrocycle motion and the main parameters governing the energy landscape of the system. Our findings could open avenues for the real-time characterization of synthetic devices at the single molecule level, and provide crucial information for designing molecular machinery able to operate under physiological conditions.

DOI

Gradient and scattering forces of anti-reflection-coated spheres in an aplanatic beam

Neng Wang, Xiao Li, Jun Chen, Zhifang Lin & Jack Ng

Anti-reflection coatings (ARCs) enable one to trap high dielectric spheres that may not be trappable otherwise. Through rigorously calculating the gradient and scattering forces, we directly showed that the improved trapping performance is due to the reduction in scattering force, which originates from the suppression of backscattering by ARC. We further applied ray optics and wave scattering theories to thoroughly understand the underlying mechanism, from which, we inferred that ARC only works for spherical particles trapped near the focus of an aplanatic beam, and it works much better for large spheres. For this reason, in contradiction to our intuition, large ARC-coated spheres are sometimes more trappable than their smaller counter parts. Surprisingly, we discovered a scattering force free zone for a large ARC-coated sphere located near the focus of an aplanatic beam. Our work provides a quantitative study of ARC-coated spheres and bridges the gap between the existing experiments and current conceptual understandings.

DOI

Photothermal-Assisted Optical Stretching of Gold Nanoparticles

Shuangshuang Wang and Tao Ding

The synergy of photothermal energy and optical forces generated by tightly focused laser beams can be used to transform the shape of gold nanoparticles. Here, the combination of these two effects is demonstrated to be an effective way of elongating gold nanoparticles (Au NPs), massively tuning their plasmonic properties. The photothermal effect of the laser increases the temperature of Au NPs above the melting point, and optical forces deform the molten Au NPs. As a result, the shape of Au NPs transforms from nanospheres into nanorods or dimers, depending on the power and time of irradiation as well as the surface energy of the substrate. This process is reversible by using high laser power to transform nanorods back to nanospheres due to capillary dewetting. Such light-induced transformations of nanostructures not only provide a facile way to tune plasmon resonances but also shed light on how the synergistic effect of photothermal energy and optical forces works on plasmonic nanoparticles.

DOI

More than two decades trapped

Cheng-Wei Qiu and Lei-Ming Zhou

Optical tweezers, crowned by Nobel Prize the first time in 1990s, have widely impacted the research landscape of atom cooling, particle manipulation/sorting, and biology. After more than two decades of steady development, it received the deserving recognition once again in 2018. Unprecedented advancements across various disciplines are believed to be spurred furthermore by this important tool of optical manipulation.

DOI

Optical Forces at Nanometer Scales

S. V. Sukhov

Advanced techniques for optical manipulation of nanoscale objects are presented. Possible mechanisms of enhancement of the effect of light on nanoobjects are listed. Enhancements by plasmon effects, field amplification in high-Q resonators, and collective effects are characterized. These methods are suitable for manipulation of various nanoobjects: quantum dots, nanowires, nanotubes, and cell organelles. Techniques for the measurement of forces at nanometer scales with atomic force microscopes are discussed.

DOI

Self-cleavage of the glmS ribozyme core is controlled by a fragile folding element

Andrew Savinov and Steven M. Block

Riboswitches modulate gene expression in response to small-molecule ligands. Switching is generally thought to occur via the stabilization of a specific RNA structure conferred by binding the cognate ligand. However, it is unclear whether any such stabilization occurs for riboswitches whose ligands also play functional roles, such as the glmS ribozyme riboswitch, which undergoes self-cleavage using its regulatory ligand, glucosamine 6-phosphate, as a catalytic cofactor. To address this question, it is necessary to determine both the conformational ensemble and its ligand dependence. We used optical tweezers to measure folding dynamics and cleavage rates for the core glmS ribozyme over a range of forces and ligand conditions. We found that the folding of a specific structural element, the P2.2 duplex, controls active-site formation and catalysis. However, the folded state is only weakly stable, regardless of cofactor concentration, supplying a clear exception to the ligand-based stabilization model of riboswitch function.

DOI

Step Sizes and Rate Constants of Single-headed Cytoplasmic Dynein Measured with Optical Tweezers

Yoshimi Kinoshita, Taketoshi Kambara, Kaori Nishikawa, Motoshi Kaya & Hideo Higuchi

A power stroke of dynein is thought to be responsible for the stepping of dimeric dynein. However, the actual size of the displacement driven by a power stroke has not been directly measured. Here, the displacements of single-headed cytoplasmic dynein were measured by optical tweezers. The mean displacement of dynein interacting with microtubule was ~8 nm at 100 µM ATP, and decreased sigmoidally with a decrease in the ATP concentration. The ATP dependence of the mean displacement was explained by a model that some dynein molecules bind to microtubule in pre-stroke conformation and generate 8-nm displacement, while others bind in the post-stroke one and detach without producing a power stroke. Biochemical assays showed that the binding affinity of the post-stroke dynein to a microtubule was ~5 times higher than that of pre-stroke dynein, and the dissociation rate was ~4 times lower. Taking account of these rates, we conclude that the displacement driven by a power stroke is 8.3 nm. A working model of dimeric dynein driven by the 8-nm power stroke was proposed.

DOI

Monday, December 3, 2018

Optical Trapping of Nanoparticles Using All-Silicon Nanoantennas

Zhe Xu, Wuzhou Song, and Kenneth B. Crozier

The ability to optically trap nanoscale particles in a reliable and noninvasive manner is emerging as an important capability for nanoscience. Different techniques have been introduced, including plasmonic nanostructures. Nano-optical tweezers based on plasmonics face the problem of Joule heating, however, due to high losses in metals. Here we experimentally demonstrate the optical trapping and transport of nanoparticles using a nonplasmonic approach, namely, a silicon nanoantenna. We trap polystyrene nanoparticles with diameters of 20 and 100 nm and use fluorescence microscopy to track their positions as a function of time. We show that multiple nanoparticles can be trapped simultaneously with a single nanoantenna. We show that the infrared trapping laser beam also produces fluorescent emission from trapped nanoparticles via two-photon excitation. We present simulations of the nanoantenna that predict enhanced optical forces with insignificant heat generation. Our work demonstrates that silicon nanoantennas enable nanoparticles to be optically trapped without deleterious thermal heating effects.

DOI

Chiral‐Plasmon‐Tuned Potentials for Atom Trapping at the Nanoscale

Zhao Chen, Fan Zhang, Xueke Duan, Tiancai Zhang, Qihuang Gong, Ying Gu

Neutral atom trapping is of importance in precision quantum metrology and quantum information processing where the atom can be viewed as an excellent frequency reference. However, creating tunable optical traps compatible with the optical nanostructures is still a challenge. Here, by introducing the chiroptical effects of a plasmonic structure into atom trapping, an active tunable potential for 3D stable optical trapping at the nanoscale is demonstrated. By altering the incident light from left‐ to right‐handed circularly polarized, the tunable range of position and potential of the trapped atoms can reach ≈60 nm and ≈0.51N mK (N denotes input power with unit mW), respectively. In addition, the blue‐detuned circularly polarized light guarantees the ultralow scattering rate and ultralong trapping lifetime. The trap centers are about hundreds of nanometers away from the structure surface, which ensures the stability of the trapping system due to the ignorable surface potential. This chiral‐based tunable atom trapping system broadens the application of chiral metamaterials and has important impact on all‐optical modulation, atomic on‐chip integration, manipulation of cold atoms, and quantum many‐body systems.

DOI

Experimental Realization of an Information Machine with Tunable Temporal Correlations

Tamir Admon, Saar Rahav, and Yael Roichman

We experimentally realize a Maxwell’s demon that converts information gained by measurements to work. Our setup is composed of a colloidal particle in a channel filled with a flowing fluid. A barrier made by light prevents the particle from being carried away by the flow. The colloidal particle then performs biased Brownian motion in the vicinity of the barrier. The particle’s position is measured periodically. When the particle is found to be far enough from the barrier, feedback is applied by moving the barrier upstream while maintaining a given minimal distance from the particle. At steady state, the net effect of this measurement and feedback loop is to steer the particle upstream while applying very little direct work on it. This clean example of a Maxwell’s demon is also naturally operated in a parameter regime where correlations between outcomes of consecutive measurements are important. Interestingly, we find a tradeoff between output power and efficiency. The efficiency is maximal at quasistatic operating conditions, whereas both the power output and rate of information gain are maximal for very frequent measurements.

DOI

Confined whispering-gallery mode in silica double-toroid microcavities for optical sensing and trapping

Huibo Fan, Xiaodong Gu, Dawei Zhou, Huili Fan, Li Fan, Changquan Xia

We propose and theoretically study a silica double-toroid microcavity to confine the whispering-gallery mode (WGM) in an ultra-small space, which consists of two toroid-to-toroid coupled cavities separated by a nanoscale gap region with low refractive index, such as the air gap. Benefitting from the strong field localization of the “slot” effect, power enhancement of symmetric WGMs in the gap results in the ultra-small mode volume of 4. which is quite smaller than the conventional toroidal microcavity with mode volume of about hundreds of cubic micrometers. The confined modes hold the potential advantages over conventional photonic devices, especially in the applications of the sensing and optical trapping. In the application of refractometer, a high refractive index sensitivity of up to 468 nm per refractive index unit (nm/RIU) can be obtained in the 1000 nm wavelength band. In the optical trapping application, the double-toroid microcavity enables a significant field enhancement in the confined WGM, and the gradient force could reach as high as 22 pN/W for a single nanoparticle with the radius of 5 nm. As the potential advantages, this study of silica double-toroid microcavity provides a good reference for realizing the high-efficient photonic applications such as optical sensing and trapping.

DOI

Optical tweezers as a mathematically driven spatio-temporal potential generator

John A. C. Albay, Govind Paneru, Hyuk Kyu Pak, and Yonggun Jun

The ability to create and manipulate spatio-temporal potentials is essential in the diverse fields of science and technology. Here, we introduce an optical feedback trap system based on high precision position detection and ultrafast feedback control of a Brownian particle in the optical tweezers to generate spatio-temporal virtual potentials of the desired shape in a controlled manner. As an application, we study the nonequilibrium fluctuation dynamics of the particle in a time-varying virtual harmonic potential and validate the Crooks fluctuation theorem in the highly nonequilibrium condition.

DOI

Wednesday, November 21, 2018

Red blood cell simulation using a coupled shell–fluid analysis purely based on the SPH method

Meisam Soleimani, Shahab Sahraee, Peter Wriggers
In this paper, a novel 3D numerical method has been developed to simulate red blood cells (RBCs) based on the interaction between a shell-like solid structure and a fluid. RBC is assumed to be a thin shell encapsulating an internal fluid (cytoplasm) which is submerged in an external fluid (blood plasma). The approach is entirely based on the smoothed particle hydrodynamics (SPH) method for both fluid and the shell structure. Both cytoplasm and plasma are taken to be incompressible Newtonian fluid. As the kinematic assumptions for the shell, Reissner–Mindlin theory has been introduced into the formulation. Adopting a total Lagrangian (TL) formulation for the shell in the realm of small strains and finite deflection, the presented computational tool is capable of handling large displacements and rotations. As an application, the deformation of a single RBC while passing a stenosed capillary has been modeled. If the rheological behavior of the RBC changes, for example, due to some infection, it is reflected in its deformability when it passes through the microvessels. It can severely affect its proper function which is providing the oxygen and nutrient to the living cells. Hence, such numerical tools are useful in understanding and predicting the mechanical behavior of RBCs. Furthermore, the numerical simulation of stretching an RBC in the optical tweezers system is presented and the results are verified. To the best of authors’ knowledge, a computational tool purely based on the SPH method in the framework of shell–fluid interaction for RBCs simulation is not available in the literature.

DOI

Acidosis affects muscle contraction by slowing the rates myosin attaches to and detaches from actin

Katelyn Jarvis, Mike Woodward, Edward P. Debold, Sam Walcott

The loss of muscle force and power during fatigue from intense contractile activity is associated with, and likely caused by, elevated levels of phosphate ( [Math Processing Error]) and hydrogen ions (decreased pH). To understand how these deficits in muscle performance occur at the molecular level, we used direct measurements of mini-ensembles of myosin generating force in the laser trap assay at pH 7.4 and 6.5. The data are consistent with a mechanochemical model in which a decrease in pH reduces myosin’s detachment from actin (by slowing ADP release), increases non-productive myosin binding (by detached myosin rebinding without a powerstroke), and reduces myosin’s attachment to actin (by slowing the weak-to-strong binding transition). Additional support of this mechanism is found by incorporating it into a branched pathway model for the effects of [Math Processing Error] on myosin’s interaction with actin. Including pH-dependence in one additional parameter (acceleration of [Math Processing Error]-induced detachment), the model reproduces experimental measurements at high and low pH, and variable [Math Processing Error], from the single molecule to large ensemble levels. Furthermore, when scaled up, the model predicts force-velocity relationships that are consistent with muscle fiber measurements. The model suggests that reducing pH has two opposing effects, a decrease in attachment favoring a decrease in muscle force and a decrease in detachment favoring an increase in muscle force. Depending on experimental details, the addition of [Math Processing Error] can strengthen one or the other effect, resulting in either synergistic or antagonistic effects. This detailed molecular description suggests a molecular basis for contractile failure during muscle fatigue.

DOI

A long overdue recognition

Arthur Ashkin has been awarded half of this year’s Nobel Prize in Physics for his invention of optical tweezers. On 2 October it was announced that the 2018 Nobel Prize in Physics was being awarded “for groundbreaking inventions in the field of laser physics”. One half of the award went to Arthur Ashkin “for the optical tweezers and their application to biological systems”, and the other half jointly to Gérard Mourou and Donna Strickland “for their method of generating high-intensity, ultra-short optical pulses”.

DOI

Processive Nanostepping of Formin mDia1 Loosely Coupled with Actin Polymerization

Hiroaki Kubota, Makito Miyazaki, Taisaku Ogawa, Togo Shimozawa, Kazuhiko Kinosita, Jr., and Shin’ichi Ishiwata

Formins are actin-binding proteins that construct nanoscale machinery with the growing barbed end of actin filaments and serve as key regulators of actin polymerization and depolymerization. To maintain the regulation of actin dynamics, formins have been proposed to processively move at every association or dissociation of a single actin molecule toward newly formed barbed ends. However, the current models for the motile mechanisms were established without direct observation of the elementary processes of this movement. Here, using optical tweezers, we demonstrate that formin mDia1 moves stepwise, observed at a nanometer spatial resolution. The movement was composed of forward and backward steps with unitary step sizes of 2.8 and −2.4 nm, respectively, which nearly equaled the actin subunit length (∼2.7 nm), consistent with the generally accepted models. However, in addition to steps equivalent to the length of a single actin subunit, those equivalent to the length of two or three subunits were frequently observed. Our findings suggest that the coupling between mDia1 stepping and actin polymerization is not tight but loose, which may be achieved by the multiple binding states of mDia1, providing insights into the synergistic functions of biomolecules for the efficient construction and regulation of nanofilaments.

DOI

A microflow velocity measurement system based on optical tweezers: A comparison using particle tracking velocimetry

Pedro Almendarez-Rangel, Beatriz Morales-Cruzado, Erick Sarmiento-Gómez, Ricardo Romero-Méndez, Francisco G.Pérez-Gutiérrez

Lab-on-a-chip devices have become useful to study substances not available in macrometric amounts. To manipulate the substances under study, ways to induce flow within such devices have been developed and, at the same time, methods to measure flow velocity have been required for the micro-scale. Several velocimetry techniques have been adapted from the macro to the micro scale, such as micro-particle image velocimetry (micro-PIV) and micro-particle tracking velocimetry (micro-PTV). However, the use of a system based on optical tweezers (OT) to measure flow velocity, specifically in microenvironments is possible. With the aim of highlighting the capabilities of an OT-based velocimetry system (OTV), we report the use of such system to measure flow velocity in a rectangular microchannel. Velocity measurements at different depths from the channel wall were carried out. As expected, an increment of the flow velocity with depth was observed. The results obtained with the OTV system were compared with measurements carried out by means of a time-averaged particle tracking velocimetry (TA-PTV). We found that both techniques provided similar results, therefore we demonstrate the capability of the OTV system to measure flow velocities in micrometric scale. The advantages of the OTV system are: (1) better space resolution, (2) minimization of the Brownian motion influence in the measurements and (3) the possibility to have submicrometric spatial resolutions without the employment of high particle concentrations, special data processing, or complex illumination systems like in other microvelocimetry techniques.

DOI

Monday, November 19, 2018

Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor

Thomas Suren, Daniel Rutz, Patrick Mößmer, Ulrich Merkel, Johannes Buchner, and Matthias Rief
The glucocorticoid receptor (GR) is a prominent nuclear receptor linked to a variety of diseases and an important drug target. Binding of hormone to its ligand binding domain (GR-LBD) is the key activation step to induce signaling. This process is tightly regulated by the molecular chaperones Hsp70 and Hsp90 in vivo. Despite its importance, little is known about GR-LBD folding, the ligand binding pathway, or the requirement for chaperone regulation. In this study, we have used single-molecule force spectroscopy by optical tweezers to unravel the dynamics of the complete pathway of folding and hormone binding of GR-LBD. We identified a “lid” structure whose opening and closing is tightly coupled to hormone binding. This lid is located at the N terminus without direct contacts to the hormone. Under mechanical load, apo-GR-LBD folds stably and readily without the need of chaperones with a folding free energy of 41kBT(24kcal/mol)41 kBT (24 kcal/mol). The folding pathway is largely independent of the presence of hormone. Hormone binds only in the last step and lid closure adds an additional 12kBT12 kBT of free energy, drastically increasing the affinity. However, mechanical double-jump experiments reveal that, at zero force, GR-LBD folding is severely hampered by misfolding, slowing it to less than 1·s−1. From the force dependence of the folding rates, we conclude that the misfolding occurs late in the folding pathway. These features are important cornerstones for understanding GR activation and its tight regulation by chaperones.

DOI

Multi-level sorting of nanoparticles on multi-step optical waveguide splitter

Xiaofu Xu, Guanghui Wang, Wenxiang Jiao, Wenbin Ji, Min Jiang, and Xuping Zhang
We propose an optofluidic sorting method for nanoparticles with different size by using optical waveguide splitter, and moreover, multiple cascaded splitters with different threshold could act as multi-level sorting unit. For a directional coupler (DC) with a specific wavelength excitation, the power splitting ratio is related to the coupling length and the gap between parallel waveguides. The power splitting ratio further determines the trapping force and potential wells distribution of both output ports. Most importantly, the potential well distribution is dependent on the particle size. For larger particles, the potential wells of both waveguides are inclined to merge, which makes it easier to be attracted and transfers to the adjacent waveguide with deeper potential well. The critical size of sorting is corresponding to the case when the barrier between wells just disappears, or the second derivative of the potential distribution is exactly zero. Moreover, since the sorting threshold of nanoparticles is related to coupling length and gap, multiple cascaded splitters with length or gap gradually varied could act as a multi-level sorting unit. A four-level sorting unit with a critical particle size of 600nm, 700nm, and 800nm are demonstrated. By considering the Brownian motion of particles and using particle-tracking method, the random distribution of nanoparticles on parallel waveguides in the sorting process is statistically presented, which agreed well with its corresponding potential wells distribution analysis. This sorting method based on multi-step optical waveguide splitter offers a number of advantages including single wavelength excitation, low loss, low power performance and ease of fabrication. This design can realize the high-throughput and large-scale nanoparticle automatic sorting in integrated photonic circuits, which have great potential for a large scale lab-on-a-chip system.

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A review of sorting, separation and isolation of cells and microbeads for biomedical applications: microfluidic approaches

Arash Dalili, Ehsan Samiei and Mina Hoorfar

Several biomedical analyses are performed on particular types of cells present in body samples or using functionalized microparticles. Success in such analyses depends on the ability to separate or isolate the target cells or microparticles from the rest of the sample. In conventional procedures, multiple pieces of equipment, such as centrifuges, magnets, and macroscale filters, are used for such purposes, which are time-consuming, associated with human error, and require several operational steps. In the past two decades, there has been a tendency to develop microfluidic techniques, so-called lab-on-a-chip, to miniaturize and automate these procedures. The processes used for the separation and isolation of the cells and microparticles are scaled down into a small microfluidic chip, requiring very small amounts of sample. Differences in the physical and biological properties of the target cells from the other components present in the sample are the key to the development of such microfluidic techniques. These techniques are categorized as filtration-, hydrodynamic-, dielectrophoretic-, acoustic- and magnetic-based methods. Here we review the microfluidic techniques developed for sorting, separation, and isolation of cells and microparticles for biomedical applications. The mechanisms behind such techniques are thoroughly explained and the applications in which these techniques have been adopted are reviewed.

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Radiation-Pressure-Antidamping Enhanced Optomechanical Spring Sensing

Fei Pan, Kaiyu Cui, Guoren Bai, Xue Feng, Fang Liu, Wei Zhang, and Yidong Huang
On-chip refractive index sensing plays an important role in many fields, ranging from chemical, biomedical, and medical to environmental applications. Recently, optomechanical cavities have emerged as promising tools for precision sensing. In view of the sensors based on optomechanical cavities, the Q factor of mechanical modes is a key parameter for achieving high sensitivity and resolution. Here we demonstrated an integrated optomechanical cavity based on a silicon nanobeam structure. Our cavity supports a fundamental mechanical mode with a frequency of 4.36 GHz and a record-high mechanical Q of 18300 in the ambient environment, facilitated by the radiation-pressure antidamping. The distinctive nature of the optomechanical spring sensing approach combined with our high mechanical Q silicon cavity allows for a sensing resolution of δλ/λ0 ∼ 10–7, which is at least 1 order of magnitude higher than that of conventional silicon-based approaches and paves the way for on-chip sensors with unprecedented sensitivity.

DOI

An optical reaction micro-turbine

Silvio Bianchi, Gaszton Vizsnyiczai, Stefano Ferretti, Claudio Maggi & Roberto Di Leonardo

To any energy flow there is an associated flow of momentum, so that recoil forces arise every time an object absorbs or deflects incoming energy. This same principle governs the operation of macroscopic turbines as well as that of microscopic turbines that use light as the working fluid. However, a controlled and precise redistribution of optical energy is not easy to achieve at the micron scale resulting in a low efficiency of power to torque conversion. Here we use direct laser writing to fabricate 3D light guiding structures, shaped as a garden sprinkler, that can precisely reroute input optical power into multiple output channels. The shape parameters are derived from a detailed theoretical analysis of losses in curved microfibers. These optical reaction micro-turbines can maximally exploit light’s momentum to generate a strong, uniform and controllable torque.

DOI

Three-dimensional tracking of microbeads attached to the tip of single isolated tracheal cilia beating under external load

Takanobu A. Katoh, Koji Ikegami, Nariya Uchida, Toshihito Iwase, Daisuke Nakane, Tomoko Masaike, Mitsutoshi Setou & Takayuki Nishizaka
To study the properties of tracheal cilia beating under various conditions, we developed a method to monitor the movement of the ciliary tip. One end of a demembranated cilium was immobilized on the glass surface, while the other end was capped with a polystyrene bead and tracked in three dimensions. The cilium, when activated by ATP, stably repeated asymmetric beating as in vivo. The tip of a cilium in effective and recovery strokes moved in discrete trajectories that differed in height. The trajectory remained asymmetric in highly viscous solutions. Model calculation showed that cilia maintained a constant net flux during one beat cycle irrespective of the medium viscosity. When the bead attached to the end was trapped with optical tweezers, it came to display linear oscillation only in the longitudinal direction. Such a beating-mode transition may be an inherent nature of movement-restricted cilia.

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Friday, November 16, 2018

Repulsion of polarized particles from two-dimensional materials

Francisco J. Rodríguez-Fortuño, Michela F. Picardi, and Anatoly V. Zayats

Repulsion of nanoparticles, molecules, and atoms from surfaces can have important applications in nanomechanical devices, microfluidics, optical manipulation, and atom optics. Here, through the solution of a classical scattering problem, we show that a dipole source oscillating at a frequency ω can experience a robust and strong repulsive force when its near-field interacts with a two-dimensional material. As an example, the case of graphene is considered, showing that a broad bandwidth of repulsion can be obtained at frequencies for which propagation of plasmon modes is allowed 0<ω<(5/3)μc, where μc is the chemical potential tunable electrically or by chemical doping.

DOI