Energetics: An emerging frontier in cellular mechanosensing: Reply to comments on “Cellular mechanosensing of the biophysical microenvironment: A review of mathematical models of biophysical regulation of cell responses”

How do cells can sense the substrate stiffness? Our recent review highlighted a range of theoretical models and simulations that have been proposed to answer this important question. In response to this review, three leading groups in the field noted some important omissions not only from our review itself but also from the field. These groups noted, correctly, that much of our understanding of cellular mechanosensing arises from models that take advantage of equilibrium thermodynamics, and that this is inappropriate because living cells are never in thermodynamic equilibrium. In this response, we highlight some promising research aimed at resolving this conundrum.