To squeeze or not: Regulation of cell size by mechanical forces in development and human diseases

Physical constraints, such as compression, shear stress, stretching and tension play major roles during development and tissue homeostasis. Mechanics directly impact physiology, and their alteration is also recognized as having an active role in driving human diseases. Recently, growing evidence has accumulated on how mechanical forces are translated into a wide panel of biological responses, including metabolism and changes in cell morphology. The aim of this review is to summarize and discuss our knowledge on the impact of mechanical forces on cell size regulation. Other biological consequences of mechanical forces will not be covered by this review. Moreover, wherever possible, we also discuss mechanosensors and molecular and cellular signaling pathways upstream of cell size regulation. We finally highlight the relevance of mechanical forces acting on cell size in physiology and human diseases. Mechanical forces, such as stretching/tension, compression, growth‐induced pressure and shear stress (blue) can be sensed and translated into cellular and physiological responses. These pathways include mechanosensitive channels (TRPV2, TRPV4), Piezo, mTOR, Hippo/YAP and autophagy (pink). Dysregulation of mechanical forces sensing and translation into a cellar response has been associated to several pathologies, such as lymphatic dysplasia, sickle cell disease, malaria, cancer, polycystic kidney disease and xerocytosis (green).