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

doi:10.1073/pnas.1705179114

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 Journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	E8618-E8627
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	41
DOIs	https://doi.org/10.1073/pnas.1705179114
Publication status	Published - 10 Oct 2017

Funding

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.

Funders	Funder number
National Science Foundation	DMR-1310266, HL86655
National Institutes of Health	P01GM096971, R01EB014703, P01HL120839
National Cancer Institute	U01CA202123
Materials Research Science and Engineering Center, Harvard University	DMR-1420570

Keywords

Cell mechanics
Cell volume
Gene expression
Molecular crowding
Stem cell fate

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1073/pnas.1705179114

Persistent URL (handle)

Persistent link

Cite this

Guo, M., Pegoraro, A. F., Mao, A., Zhou, E. H., Arany, P. R., Han, Y., Burnette, D. T., Jensen, M. H., Kasza, K. E., Moore, J. R., Mackintosh, F. C., Fredberg, J. J., Mooney, D. J., Lippincott-Schwartz, J., & Weitz, D. A. (2017). Cell volume change through water efflux impacts cell stiffness and stem cell fate. Proceedings of the National Academy of Sciences of the United States of America, 114(41), E8618-E8627. https://doi.org/10.1073/pnas.1705179114

@article{4161be7f156b4251812e13a281a9529c,

title = "Cell volume change through water efflux impacts cell stiffness and stem cell fate",

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.",

keywords = "Cell mechanics, Cell volume, Gene expression, Molecular crowding, Stem cell fate",

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

year = "2017",

month = oct,

day = "10",

doi = "10.1073/pnas.1705179114",

language = "English",

volume = "114",

pages = "E8618--E8627",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "41",

}

Guo, M, Pegoraro, AF, Mao, A, Zhou, EH, Arany, PR, Han, Y, Burnette, DT, Jensen, MH, Kasza, KE, Moore, JR, Mackintosh, FC, Fredberg, JJ, Mooney, DJ, Lippincott-Schwartz, J & Weitz, DA 2017, 'Cell volume change through water efflux impacts cell stiffness and stem cell fate', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 41, pp. E8618-E8627. https://doi.org/10.1073/pnas.1705179114

TY - JOUR

T1 - Cell volume change through water efflux impacts cell stiffness and stem cell fate

AU - Guo, Ming

AU - Pegoraro, Adrian F.

AU - Mao, Angelo

AU - Zhou, Enhua H.

AU - Arany, Praveen R.

AU - Han, Yulong

AU - Burnette, Dylan T.

AU - Jensen, Mikkel H.

AU - Kasza, Karen E.

AU - Moore, Jeffrey R.

AU - Mackintosh, Frederick C.

AU - Fredberg, Jeffrey J.

AU - Mooney, David J.

AU - Lippincott-Schwartz, Jennifer

AU - Weitz, David A.

PY - 2017/10/10

Y1 - 2017/10/10

N2 - 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.

AB - 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.

KW - Cell mechanics

KW - Cell volume

KW - Gene expression

KW - Molecular crowding

KW - Stem cell fate

UR - http://www.scopus.com/inward/record.url?scp=85030758744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030758744&partnerID=8YFLogxK

U2 - 10.1073/pnas.1705179114

DO - 10.1073/pnas.1705179114

M3 - Article

AN - SCOPUS:85030758744

SN - 0027-8424

VL - 114

SP - E8618-E8627

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 41

ER -

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

Abstract

Funding

Keywords

UN SDGs

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this