Compressive Stress Stalls Growth and Decreases Cytoplasmic Diffion

Abstract

Any cell population growing in a limited space can generate mechanical compressive stresses. Tumors growing within tissues and microbes that are naturally confined by their environment both build up growth-induced pressure. While the effects of tensile mechanical stresses have been widely studied, much less is known about the effects of compressive mechanical stresses on cell physiology. We developed a microfluidic mechano-chemostat that enables a precise temporal control of mechanical and chemical conditions. We found that rate of cell growth is affected by compressive stress: Cell growth decreased exponentially with pressure. In order to investigate the molecular origin for such a growth decrease, we developed genetically encoded multimeric nanoparticles (GEMs) to assess the regulation of cellular crowding and the effects of a mechanical compressive stress on cell microrheology. GEMs are particles of 16nm or 35 nm in size naturally expressed by cells that enable direct particle tracking. We observe that the motion of GEMs is non-ergodic and subdiffusive, and that crowding is highly regulated in a cell by the regulation of ribosome biogenesis. Moreover, similar to overall growth-rate, GEM diffusion follows the same exponentially decreased with increasing compressive stress that growth rate. To conclude, we speculate that macromolecular diffusion becomes rate limiting for growth under compressive stress. Intermediate mechanical stresses could drive changes in crowding and diffusion to regulate cell physiology, from metabolism to signaling.