EML webinar overview: Mechanical stresses kill tumor cells. (November 2021) - Sheetz, Michael
Abstract: The field of Mechanobiology is in its infancy in that we are just starting to appreciate the molecular processes used by cells to mechanically create the form of organisms. These are robust processes that use stochastic diffusion to deterministically create shapes that have been selected through billions of years of evolution (for background see The Cell as a Machine, M. Sheetz and H. Yu, Cambridge Press, 2018. DOI http://dx.doi.org/10.1017/9781107280809 [10.1017/9781107280809]). One mechanosensing process that is partially understood is the sensing of matrix rigidity. Cell rigidity sensors are roughly two micron sarcomeric structures that pull matrix contacts by a constant displacement of about 100 nm and the force then indicates the rigidity. A major role of this process is to block unwanted adult cell growth on soft surfaces; but in wound-healing, rigidity sensors are lost to enable adult cell growth. If the sensors are not restored upon healing, tumorigenic (transformed) growth on soft surfaces occurs leading to severe cancers if other factors are added such as immortality, and vascularization. Our surprising finding is that transformed cells are mechanically sensitive and will die if repeatedly stretched or exposed to ultrasound. Since nearly all tumor cells are transformed, mechanical therapies can inhibit the growth of most cancers. This provides a novel application of mechanotherapy in fighting cancer.