Chrysovalantou KALAITZIDOU

Data-integrated Multiscale Modelling of Fibrous Extracellular Matrix

Living tissues are not just collections of packed cells. Much of a tissue’s capacity consists of extracellular space which is largely filled by a complex meshwork, the Extracellular Matrix (ECM). Many cells bind to components of the extracellular matrix, which are mainly fibrous proteins (fibers). This cell-to-ECM adhesion is regulated by specific cell-surface cellular adhesion molecules. When cells contract, i.e. reduce their volume, they exert loads on the fibers they attach to and thereby deforming their extracellular space. The induced force fields serve as signals to other cells, facilitating intercellular interactions. As a respond to these signals, neighboring cells can detect and even approach each other. The effects of these interactions include differentiation tendency of stem cells, as well as cell migration and regeneration. Understanding the mechanism underlying the deformations that drive these phenomena is equivalent to characterising the mechanical properties of ECM. In the current study, we implement a two dimensional discrete model of a fiber network to capture localized deformations induced by one or two contracting cells. We develop constitutive models, for which the stored energy function of the network is formulated by starting from a nonlinear force-stretch relation of a single fiber. Our models are able to capture predictions from previously conducted experiments, including enhanced fiber alignment and the formation of densified bands connecting two contractile cells, mechanisms that have been associated with cell-cell mechanical communication.

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