Fibrin network adaptation to cell-generated forces

Fransisca A. S. van Esterik, Arianne V. Vega, Kristian A. T. Pajanonot, Daniel R. Cuizon, Michelle E. Velayo, Jahazel Dejito, Stephen L. Flores, Jenneke Klein-Nulend, Rommel G. Bacabac

Fibrin promotes wound healing by serving as provisional extracellular matrix for fibroblasts that realign and degrade fibrin fibers, and sense and respond to surrounding substrate in a mechanical-feedback loop. We aimed to study mechanical adaptation of fibrin networks due to cell-generated forces at the micron-scale. Fibroblasts were elongated-shaped in networks with ≤ 2 mg/ml fibrinogen, or cobblestone-shaped with 3 mg/ml fibrinogen at 24 h. At frequencies f < 102 Hz, G′ of fibroblast-seeded fibrin networks with ≥ 1 mg/ml fibrinogen increased compared to that of fibrin networks. At frequencies f > 103 Hz, G″ of fibrin networks decreased with increasing concentration following the power-law in frequency with exponents ranging from 0.75 ± 0.03 to 0.43 ± 0.03 at 3 h, and of fibroblast-seeded fibrin networks with exponents ranging from 0.56 ± 0.08 to 0.28 ± 0.06. In conclusion, fibroblasts actively contributed to a change in viscoelastic properties of fibrin networks at the micron-scale, suggesting that the cells and fibrin network mechanically interact. This provides better understanding of, e.g., cellular migration in wound healing.

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