Cells exploit a phase transition to establish interconnections in fibrous extracellular matrices

Abstract

By exerting mechanical forces, biological cells generate striking spatial patterns of localised deformation in the surrounding collagen network. Tethers-paths of high densification and fiber alignment-form between cells, and radial hair-like bands emanate from cell clusters. While tethers facilitate cell communication, the mechanism for their formation is unclear. Here we combine modelling, simulation and experiment, and explore unexpected similarities with martensitic microstructures in shape memory alloys; we show that tether formation is a densification phase transition of the fibrous extracellular matrix, caused by buckling instability of network fibers under cell-induced compression. Our model uses multiscale averaging over fiber orientations to obtain a two-phase, bistable continuum strain energy density for fibrous collagen, with a densified second phase. Simulations predict strain discontinuities between the undensified and the densified phase, which localises within intercellular tethers and radial emanations from cell clusters, as experimentally observed. Ruling out biochemical factors, our experiments use contracting active hydrogel particles to produce similar-but controlled-localised deformations as contractile cells. Our results reveal subtle connections with martensitic phase transitions that demonstrate how, by exploiting a special instability, cells spontaneously generate pathways to each other in a 3D complex medium simply by contracting, with implications on intercellular mechanosensing and the remodelling of matrix mechanical properties by tether networks.