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Mechanics of collagen networks with active cellular inclusions
Tissues are composed of extracellular matrix (ECM) and cells that are in constant interplay. While ECM influences many cellular processes from division and migration to differentiation, cells interact with their surrounding environment by exerting pulling forces, and remodelling or degrading the matrix, thus altering its structural and rheological properties. How these local matrix changes originated by the cells affect the overall global mechanics of tissues is not fully understood yet. Furthermore, a clear disentangling between the contributions of passive mechanical effects versus active cellular effects to tissue mechanics is still lacking. Here, we address this question by investigating how local cell-matrix interactions regulate the global mechanics of collagen networks in a biomimetic tissue model composed of fibrillar collagen type I with embedded invasive cancer cells (MDA-MB-231). We find by bulk shear rheology that above a cell volume fraction of only a few percents, the mechanics of the collagen network is strongly affected. We observe a softening both of the mature network and over time during collagen polymerization, as well as a loss of the classic stress-stiffening behaviour of collagen. We decouple passive and active contributions by using cell-sized passive inclusions, blocking cell adhesion and contractility, and through rheo-confocal microscopy for simultaneous rheology measurements and in situ visualisation. Our findings bring insights into how active inclusions alter the mechanics of fibrous networks, contributing to a better understanding of the role of cells in the mechanics of healthy but also diseased tissues.