Mechanical feedback cycles determine the function and self-organization of cells and tissues in space and time. Such feedback is determined by internal and external mechanical cues that are linked through signaling pathways to cellular processes that again result in remodeling of mechanical cues. Since studying these feedback cycles in vivo has been very difficult, we use advanced in vitro models. They offer the unique opportunity to alter single mechanical cues in well-defined ways and to dissect their effects under otherwise identical conditions. It allows to elucidate aspects of the mechanobiological feedback that is crucial for controlling tissue adaptation, differentiation, and function. The understanding of these processes is a prerequisite for rational management of tissue engineering and the prevention of disease progression.

The scheme emphasizes the two-pronged remodeling processes, which involve both the epithelium itself and its underlying multicomponent extracellular matrix. The resulting changes in force distribution, stiffness, shape, and structure determine epithelial adaptation, differentiation, and function, which are, in turn, coupled to remodeling of the epithelium and the extracellular matrix through parallel feedback loops.