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Thursday, August 23, 2012

Filopodium retraction is controlled by adhesion to its tip

Stephane Romero, Alessia Quatela, Thomas Bornschlögl, Stéphanie Guadagnini, Patricia Bassereau and Guy Tran Van Nhieu

Filopodia are thin cell extensions sensing the environment. They play an essential role during cell migration, cell-cell or cell-matrix adhesion, by initiating contacts and conveying signals to the cell cortex. Pathogenic microorganisms can hijack filopodia to invade cells by inducing their retraction towards the cell body. Because their dynamics depend on a discrete number of actin filaments, filopodia provide a model of choice to study elementary events linked to adhesion and downstream signaling. However, the determinants controlling filopodial sensing are not well characterized. Here, we have used beads functionalized with different ligands that triggered filopodial retraction when contacting filopodia of epithelial cells. With optical tweezers (OTs), we were able to measure forces stalling the retraction of a single filopodium. We found that the filopodial stall force depends on the coating of the bead. Stall forces reached 8 pN for beads coated with the β1- integrin ligand Yersinia Invasin, while retraction was stopped with a higher force of 15 pN when beads were functionalized with carboxyl groups. In all cases, stall forces increased in correlation with the density of ligands contacting filopodial tips and were independent of the optical trap stiffness. Unexpectedly, a discrete and small number of Shigella type three secretion systems induced stall forces of 10 pN. These results suggest that the number of receptor-ligand interactions at the filopodial tip determines the maximal retraction force exerted by filopodia but a discrete number of clustered receptors is sufficient to induce high retraction stall forces.

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