Nonlinear Elasticity of the Fibers Contained in the ECM Facilitates Efficient Inter-cellular Mechanical Signalling

Background: Cell-generated mechanical forces are conveyed through the extracellular matrix (ECM), which allows long-range intercellular mechanical signalling. This form of communication is augmented by the formation of intercellular bands of dense and aligned fibers, which plays a pivotal role in various biological processes. This study was aimed to explore the effects of elastic nonlinearity of the ECM fibers on the transmission of loads between contracting cells.

Methods: A finite-element model of two cells contracting within a fibrous network was developed based on our biological experiments. The fibers were modeled as showing linear elasticity, compression microbuckling and/or tension stiffening.

Results: Fiber buckling resulted in smaller loads (strains and stresses) in the peri-cell ECM, which were primarily directed toward the neighboring cell. These loads decreased with increasing cell-to-cell distance and dissipated when cells were >9 cell diameters apart. Tension stiffening further contributed to directing the loads toward the neighboring cell, though to a smaller extent. The contraction of two cells resulted in mutual attraction forces, which were considerably increased by tension stiffening. Nonlinear elasticity contributed also to the onset of force polarity on the cell boundaries. The density and alignment of the fibers within the intercellular band were greater when fibers buckled under compression, with tension stiffening further contributing to such structural remodeling.

Conclusion: Directional and efficient transfer of mechanical signals between distant cells is facilitated by nonlinear elasticity of the ECM fibers. Our findings rehighlight the importance of using fibrous gels – rather than synthetic ones – in experimental research settings.