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Burnette Lab

Cell volume change through water efflux impacts cell stiffness and stem cell fate.

AUTHORS

Guo MMing , Pegoraro AF Adrian F , Mao A Angelo , Zhou EH Enhua H , Arany PR Praveen R , Han Y Yulong , Burnette DT Dylan T , Jensen MH Mikkel H , Kasza KE Karen E , Moore JR Jeffrey R , Mackintosh FC Frederick C , Fredberg JJ Jeffrey J , Mooney DJ David J , Lippincott-Schwartz J Jennifer , Weitz DA David A . Proceedings of the National Academy of Sciences of the United States of America. 2017 10 10; 114(41). E8618-E8627

ABSTRACT

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology.

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology.