Modeling Cellular Adaptation to Mechanical Stress
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It is well-accepted that cyclic circumferential stretching of the arterial wall regulates endothelial cell form and function, with the actin cytoskeleton playing a central role. While there has been much progress in characterizing the contribution of the actin cytoskeleton to cellular mechanical properties and to mechanotransduction, it is not well understood how cell mechanical properties influence mechanotransduction. Further, the ability of actin filaments to assemble and disassemble renders the mechanical properties of the actin cytoskeleton highly dynamic. It is suggested herein that endothelial cells can adapt to certain patterns of stretch through directed cytoskeletal remodeling to minimize stretch-induced stress, and this in turn alters the activity of stretch-induced signaling events. A continuum adaptive constitutive model, formulated using mixture theory and motivated by cellular microstructure, is proposed in order to predict the initial stresses developed in stretched adherent cells, and the ensuing microstructural changes which act to minimize intracellular stresses as the actin cytoskeleton remodels. An experimental system is described for testing the model and predictions are made for the time evolution of intracellular stresses, actin organization and mechanotransduction in endothelial cells subjected to different patterns of stretch, which correlate with experimentally observed results. 2008 Springer-Verlag.
