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

Ming Guo, Adrian F. Pegoraro, Angelo Mao, Enhua H. Zhou, Praveen R. Arany, Yulong Han, Dylan T. Burnette, Mikkel H. Jensen, Karen E. Kasza, Jeffrey R. Moore, Frederick C. Mackintosh, Jeffrey J. Fredberg, David J. Mooney, Jennifer Lippincott-Schwartz*, David A. Weitz

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)E8618-E8627
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
Publication statusPublished - 10 Oct 2017


ACKNOWLEDGMENTS. We thank J. P. Butler, F. Deng, and A. E. Ehrlicher for helpful discussions. This work was supported by NIH Grants P01GM096971, P01HL120839, and R01EB014703; Harvard Materials Research Science and Engineering Center Grant DMR-1420570; and NSF Grant DMR-1310266. M.H.J. and J.R.M. were supported by NIH Grant HL86655.

FundersFunder number
National Science FoundationDMR-1310266, HL86655
National Institutes of HealthP01GM096971, R01EB014703, P01HL120839
National Cancer InstituteU01CA202123
Materials Research Science and Engineering Center, Harvard UniversityDMR-1420570


    • Cell mechanics
    • Cell volume
    • Gene expression
    • Molecular crowding
    • Stem cell fate


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