Intercellular mechanical signalling in a 3D nonlinear fibrous network model

Abstract

The extracellular matrix (ECM) consists of a network of polymeric fibres in which cells are embedded and interact with each other. The nonlinear elasticity of the ECM aids in directing the transmission of cell-induced mechanical loads over long distances, thereby facilitating mechanical communication between cells that are not in direct contact. Previous computational models have established the role of compression-buckling of the ECM fibres in increasing the propagation range of mechanical loads and fibre remodelling, however, most of them are two-dimensional (2D). Here, we generate a more realistic, 3D finite-element simulation of two cells contracting within the ECM by means of two contractile spheres embedded within a network of beam elements. We explore the effects of the mechanical behaviour of the fibres (linear-elastic, compression-bucklable), network connectivity (3.7, 8, 12) and intercellular distance (1–5 cell radii) on the structural remodelling and mechanical loads occurring on the cell surface and within the intercellular region of the ECM. When cells were embedded in a matrix of bucklable rather than linear-elastic fibres, contraction-induced loads were more directed towards the neighbouring cell, and the fibre rearrangement in the intercellular ECM was more eminent up to an intercellular distance of ∼2.5–5 cell radii. Our 3D discrete model highlights the role of the ECM nonlinear elasticity in the efficient transfer of mechanical signals between cells, a mechanism governing numerous multicellular processes such as tissue morphogenesis, wound healing, angiogenesis and cancer metastasis. The findings reemphasise the importance of using nonlinear elastic gels in in vitro cellular models.