Elastic Anisotropy Governs the Decay of Cell-induced Displacements

Abstract

The unique nonlinear mechanics of the fibrous extracellular matrix (ECM) facilitates long-range cell-cell mechanical communications that would be impossible on linear elastic substrates. Past research has described the contribution of two separated effects on the range of force transmission, including ECM elastic non-linearity and fiber alignment. However, the relation between these different effects is unclear, and how they combine to dictate force transmission range is still elusive. Here, we combine discrete fiber simulations with continuum modeling to study the decay of displacements induced by a contractile cell in fibrous networks. We demonstrate that fiber non-linearity and fiber reorientation both contribute to the strain-induced anisotropy of the elastic moduli of the cell local environment. This elastic anisotropy is a parameter that governs the slow decay of the displacements, and it depends on the magnitude of applied strain, either an external tension or an internal contraction as a model of the cell. Furthermore, we show that accounting for artificially-prescribed elastic anisotropy dictates the displacement decay induced by a contracting cell. Our findings unify previous single effects into a mechanical theory that explains force transmission in fibrous networks. This work provides important insights into biological processes that involve the coordinated action of distant cells mediated by the ECM, such that occur in morphogenesis, wound healing, angiogenesis, and cancer metastasis. It may also provide design parameters for biomaterials to control force transmission between cells, as a way to guide morphogenesis in tissue engineering.