|Many cellular reactions are controlled or mediated by mechanical forces. Cells probe the mechanical properties of their environment and subsequently transduce this information accurately into a specific molecular response: mechanical cues can determine the fate of stem cells, modulate the function of entire tissues and play a key role in various pathologies. Cells also alter their motility and metabolic functions depending on the mechanics of their surroundings. Strikingly, cells are not passive observers of the mechanical properties – many cells actively manipulate their surroundings either by the generation of new extracellular or pericellular materials or, even by exerting forces on the outside world. The physical mechanisms by which cells sense tissue rigidity, respond to it, and apply forces themselves are poorly understood and has been little studied by physicists. We aim to elucidate fundamental principles of force production and mechanosensing of cells. Specifically, the program will focus on the following two key questions:
These questions are obviously of considerable fundamental interest. While the concept and the relevance of mechanical sensing and transduction of cells are firmly established, relatively little is known about how, precisely, the key molecular elements interact and together establish and optimize mechanosensory pathways. Progress in this area has been held back by the fundamentally interdisciplinary nature of the problem. Our program is explicitly designed to bring about a fundamental understanding of the physical basis of cellular mechanosensing and mechanotransduction by joining groups from physics and biology together in a focused effort.
In addition to the basic science promise, our program explores new horizons in the mechanical control of cell function and cell fate. Mechanical sensing and transduction pathways are fundamentally generic in the sense that the signal they convey is not generated, transported and interpreted in highly redundant and degenerate processes such as, for instance, in many biochemical sensory pathways or metabolic networks. Rather, similar physical mechanisms are at play in each mechanical signaling chain. A comprehensive and in-depth understanding of the processes involved will have immediate, and urgently needed, impact on the understanding of pathologies and malfunctioning of mechanical driven pathways. Our research program is aimed at understanding the role and interactions of the key proteins and processes, and as such has the potential to help identify novel molecular targets.