Biosynthetic solutions to mechanical stress: why do mechanical stresses drive altered metabolism?

Cells reside in mechanically stressful microenvironments where protrusive and traction forces from neighboring cells and cell-intrinsic forces derived from adhesions to the extracellular matrix (ECM) establish a dynamical "Mechanoreciprocity". Mechanoreciprocity is the concept that cells respond to the physical properties of the cellular microenvironment by reciprocally exerting proportional forces [1]. However, if feed-forward mechanical stress responses based on energetically demanding cytoskeletal dynamics are the only ways cells reciprocally respond to physical cues, we would not observe the force-induced thickening of bone [2] or hypertension-associated collagen accumulation in the kidney [3]. These processes are examples of adaptive biosynthetic responses by cells that may serve to buffer mechanical stresses in energetically efficient ways. In this review, we will introduce some of the ways in which cells respond to the physical properties of the microenvironment and suppose why these observed metabolic changes serve to support biosynthetic solutions to buffer mechanical stresses, a response that can preserve tissue structure or, in excess, distort it.