Cell reorientation under cyclic stretching

Mechanical cues from the extracellular microenvironmen​t play a central role in regulating the structure, function and fate of living cells. Nevertheless, the precise nature of the mechanisms and processes underlying this crucial cellular mechanosensitiv​ity remains a fundamental open problem. Here we provide a novel framework for addressing cellular sensitivity and response to external forces by experimentally and theoretically studying one of its most striking manifestations – cell reorientation to a uniform angle in response to cyclic stretching. We first report on extensive new experiments of adherent cell reorientation under cyclic stretching and show that they cannot be quantitatively explained by existing models. We then propose a new theory which focuses on the cell’s stored elastic energy, corresponding to a 2D anisotropic linear elastic material. The variation of this energy with the cell’s orientation is shown to drive the dissipative reorientation process. Our theory is in excellent quantitative agreement with the complete temporal reorientation dynamics of individual cells, measured over a wide range of experimental conditions, thus elucidating a basic aspect of mechanosensitiv​ity. It, moreover offers new venues for predicting and controlling cell behavior in response to mechanical cues from the microenvironmen​t.