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.

细胞如何感知底物的刚度？我们最近的评论强调了为回答这个重要问题而提出的一系列理论模型和模拟。针对此审查，该领域的三个领导小组不仅注意到我们的审查本身，而且指出了该领域的一些重要遗漏。这些小组正确地指出，我们对细胞机械传感的大部分理解都来自利用平衡热力学的模型，这是不适当的，因为活细胞从未处于热力学平衡状态。在此回应中，我们重点介绍了一些有希望解决该难题的研究。