| The role of mechanics in cell biology is important, both as a cellular stimulus and effect. For example, cell shape, as well as the number and force of extracellular matrix adhesions, control cell fate. In this case, forces are transduced into chemical signals that ultimately affect a cellular response (mechanotransduction). Similarly, the chemical binding of ions to specialized types of membrane motor proteins can elicit mechanical deformations, and under the right conditions, mechanical force. In the latter example, the cell itself produces a mechanical output. Here, a coordinated study incorporating experimental, theoretical, and computational approaches is proposed to investigate mechanical and electro-mechanical transduction in cells. In order to examine the effect of forces acting on a cell, the cell adhesion-cytoskeleton-nucleus mechanical pathway in the context of endothelial cell rounding is considered. We measured nuclear stretch as a result of endothelial cell rounding, theoretically estimated the forces acting on the nucleus, and followed up with computational modeling of the cell rounding event. We found that forces associated with loss of cytoskeletal pre-tension were mostly responsible for the nuclear deformation, and our computed nuclear stress maps can be used to understand mechanotransduction at the site of the nucleus. The electro-mechanical transduction of the specialized mammalian outer hair cell was analyzed for the case of a cellular mechanical effect. First, we compared two methods estimating the local moduli of the outer hair cell, and showed that under certain conditions, the estimates of both methods overlap. Next, we derived the energies and efficiency involved in outer hair cell electro-mechanical transduction. This investigation presents two very interesting problems in cellular biomechanics: the generation of force from prestin-Cl-binding; and, mechanotransduction at the nucleus due through the adhesion-cytoskeleton-nucleus pathway. |
