Cells that proliferate within a confined environment build up mechanical<br> compressive stress. For example, mechanical pressure emerges in the<br> naturally space-limited tumor environment. However, little is known<br> about how cells sense and respond to mechanical compression. We<br> developed microfluidic bioreactors to enable the investigation of the<br> effects of compressive stress on the growth of the genetically tractable<br> model organism Saccharomyces cerevisiae. We used this system to<br> determine that compressive stress is partly sensed through a module<br> consisting of the mucin Msb2 and the cell wall protein Sho1, which act<br> together as a sensor module in one of the two major osmosensing pathways<br> in budding yeast. This signal is transmitted via the MAPKKK kinase<br> Ste11. Thus, we term this mechanosensitive pathway the "SMuSh" pathway,<br> for Ste11 through Mucin/Sho1 pathway. The SMuSh pathway delays cells in<br> the G1 phase of the cell cycle and improves cell survival in response to<br> growth-induced pressure. We also found that the cell wall integrity<br> (CWI) pathway contributes to the response to mechanical compressive<br> stress. These latter results are confirmed in complimentary experiments<br> in Mishra et al. [Mishra R, et al. (2017) Proc Natl Acad Sci USA,<br> 10.1073/pnas. 1709079114]. When both the SMuSh and the CWI pathways are<br> deleted, cells fail to adapt to compressive stress, and all cells lyse<br> at relatively low pressure when grown in confinement. Thus, we define a<br> network that is essential for cell survival during growth under<br> pressure. We term this mechanosensory system the SCWISh (survival<br> through the CWI and SMuSh) network.