  Mechanical cues from the extracellular microenvironment 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 mechanosensitivity 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 of the underlying substrate. We first show that existing approaches
are incompatible with our extensive measurements of cell reorientation. We then
propose a fundamentally new theory that shows that dissipative relaxation of
the cell's passively-stored, two-dimensional, elastic energy to its minimum
actively drives the 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 mechanosensitivity.
