DOI: 10.1242/jcs.108886. Matrix stiffness reverses the effect of actomyosin tension on cell proliferation

Matrix stiffness reverses the effect of actomyosin tension on cell proliferation

10.1242/jcs.108886

Crossref journal-article

The Company of Biologists

Journal of Cell Science (237)

Abstract

Summary The stiffness of the extracellular matrix exerts powerful effects on cell proliferation and differentiation, but the mechanisms transducing matrix stiffness into cellular fate decisions remain poorly understood. Two widely reported responses to matrix stiffening are increases in actomyosin contractility and cell proliferation. To delineate their relationship, we modulated cytoskeletal tension in cells grown across a physiological range of matrix stiffnesses. On both synthetic and naturally derived soft matrices, and across a panel of cell types, we observed a striking reversal of the effect of inhibiting actomyosin contractility, switching from the attenuation of proliferation on rigid substrates to the robust promotion of proliferation on soft matrices. Inhibiting contractility on soft matrices decoupled proliferation from cytoskeletal tension and focal adhesion organization, but not from cell spread area. Our results demonstrate that matrix stiffness and actomyosin contractility converge on cell spreading in an unexpected fashion to control a key aspect of cell fate.

Bibliography

Mih, J. D., Marinkovic, A., Liu, F., Sharif, A. S., & Tschumperlin, D. J. (2012). Matrix stiffness reverses the effect of actomyosin tension on cell proliferation. Journal of Cell Science, 125(24), 5974â5983.

Authors 5

Justin D. Mih (first)
Aleksandar Marinkovic (additional)
Fei Liu (additional)
Asma S. Sharif (additional)
Daniel J. Tschumperlin (additional)

References 55 Referenced 173

10.1016/j.cub.2010.05.049 / Curr. Biol. / Transient frictional slip between integrin and the ECM in focal adhesions under myosin II tension. by Aratyn–Schaus (2010)
10.1016/j.tcb.2008.05.002 / Trends Cell Biol. / Growth control by intracellular tension and extracellular stiffness. by Assoian (2008)
10.1038/35074532 / Nat. Cell Biol. / Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. by Balaban (2001)
10.1038/nrc2544 / Nat. Rev. Cancer / A tense situation: forcing tumour progression. by Butcher (2009)
10.1152/ajpcell.00270.2001 / Am. J. Physiol. Cell Physiol. / Traction fields, moments, and strain energy that cells exert on their surroundings. by Butler (2002)
10.1529/biophysj.106.084806 / Biophys. J. / Nonmuscle myosin IIA-dependent force inhibits cell spreading and drives F-actin flow. by Cai (2006)
10.1007/s12195-010-0102-6 / Cell Mol. Bioeng. / Substrate stiffness and cell area predict cellular traction stresses in single cells and cells in contact. by Califano (2010)
10.1126/science.276.5317.1425 / Science / Geometric control of cell life and death. by Chen (1997)
10.1016/S0955-0674(98)80145-2 / Curr. Opin. Cell Biol. / Cellular control lies in the balance of forces. by Chicurel (1998)
10.1371/journal.pone.0015655 / PLoS ONE / Soft substrates promote homogeneous self-renewal of embryonic stem cells via downregulating cell-matrix tractions. by Chowdhury (2010)
10.1126/science.1116995 / Science / Tissue cells feel and respond to the stiffness of their substrate. by Discher (2005)
10.1242/jcs.114.18.3285 / J. Cell Sci. / Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors. by Dugina (2001)
10.1038/273345a0 / Nature / Role of cell shape in growth control. by Folkman (1978)
10.1074/jbc.M101898200 / J. Biol. Chem. / Fibroblast quiescence in floating or released collagen matrices: contribution of the ERK signaling pathway and actin cytoskeletal organization. by Fringer (2001)
10.1038/nmeth.1487 / Nat. Methods / Mechanical regulation of cell function with geometrically modulated elastomeric substrates. by Fu (2010)
10.1083/jcb.200204153 / J. Cell Biol. / The relationship between force and focal complex development. by Galbraith (2002)
10.1038/nrm2593 / Nat. Rev. Mol. Cell Biol. / Environmental sensing through focal adhesions. by Geiger (2009)
10.1152/japplphysiol.01121.2004 / J. Appl. Physiol. / Cell type-specific response to growth on soft materials. by Georges (2005)
10.1016/j.biomaterials.2006.09.038 / Biomaterials / Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties. by Ghosh (2007)
10.1091/mbc.E02-08-0493 / Mol. Biol. Cell / Dendritic fibroblasts in three-dimensional collagen matrices. by Grinnell (2003)
10.1016/j.stem.2009.06.016 / Cell Stem Cell / Control of stem cell fate by physical interactions with the extracellular matrix. by Guilak (2009)
10.1529/biophysj.105.070144 / Biophys. J. / Substrate rigidity regulates the formation and maintenance of tissues. by Guo (2006)
10.1083/jcb.200511093 / J. Cell Biol. / Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. by Hotulainen (2006)
10.1091/mbc.9.11.3179 / Mol. Biol. Cell / Control of cyclin D1, p27(Kip1), and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. by Huang (1998)
10.1038/13043 / Nat. Cell Biol. / The structural and mechanical complexity of cell-growth control. by Huang (1999)
10.1016/j.cub.2009.07.069 / Curr. Biol. / Cell-cycle control by physiological matrix elasticity and in vivo tissue stiffening. by Klein (2009)
10.1038/sj.bjp.0701668 / Br. J. Pharmacol. / The mechanism of action of cantharidin in smooth muscle. by Knapp (1998)
10.1073/pnas.0405873102 / Proc. Natl. Acad. Sci. USA / FRET measurements of cell-traction forces and nano-scale clustering of adhesion ligands varied by substrate stiffness. by Kong (2005)
10.1038/ncb2216 / Nat. Cell Biol. / Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. by Kuo (2011)
10.1016/j.cell.2009.10.027 / Cell / Matrix crosslinking forces tumor progression by enhancing integrin signaling. by Levental (2009)
10.1083/jcb.201004082 / J. Cell Biol. / Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression. by Liu (2010)
10.1016/S0006-3495(00)76279-5 / Biophys. J. / Cell movement is guided by the rigidity of the substrate. by Lo (2000)
10.1074/jbc.M402725200 / J. Biol. Chem. / Role of RhoA, mDia, and ROCK in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition. by Mammoto (2004)
10.1016/j.ceb.2009.08.001 / Curr. Opin. Cell Biol. / Cytoskeletal control of growth and cell fate switching. by Mammoto (2009)
10.1152/ajplung.00108.2012 / Am. J. Physiol. Lung Cell. Mol. Physiol. / Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness. by Marinković (2012)
10.1016/S1534-5807(04)00075-9 / Dev. Cell / Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. by McBeath (2004)
10.1371/journal.pone.0019929 / PLoS ONE / A multiwell platform for studying stiffness-dependent cell biology. by Mih (2011)
10.1016/j.devcel.2010.07.018 / Dev. Cell / Stretchy proteins on stretchy substrates: the important elements of integrin-mediated rigidity sensing. by Moore (2010)
10.1038/385537a0 / Nature / Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. by Palecek (1997)
10.1083/jcb.200906012 / J. Cell Biol. / Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylation. by Pasapera (2010)
10.1016/j.ccr.2005.08.010 / Cancer Cell / Tensional homeostasis and the malignant phenotype. by Paszek (2005)
10.1242/jcs.067009 / J. Cell Sci. / Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling. by Provenzano (2011)
10.1073/pnas.0608030104 / Proc. Natl. Acad. Sci. USA / Microtubule function in fibroblast spreading is modulated according to the tension state of cell-matrix interactions. by Rhee (2007)
10.1529/biophysj.107.116863 / Biophys. J. / Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation. by Roca–Cusachs (2008)
10.1529/biophysj.105.071217 / Biophys. J. / Is the mechanical activity of epithelial cells controlled by deformations or forces? by Saez (2005)
10.1073/pnas.1017474108 / Proc. Natl. Acad. Sci. USA / Myosin-II inhibition and soft 2D matrix maximize multinucleation and cellular projections typical of platelet-producing megakaryocytes. by Shin (2011)
10.1529/biophysj.106.101386 / Biophys. J. / Fibroblast adaptation and stiffness matching to soft elastic substrates. by Solon (2007)
10.1126/science.1081412 / Science / Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor. by Straight (2003)
10.1371/journal.pone.0012905 / PLoS ONE / Matrix rigidity regulates cancer cell growth and cellular phenotype. by Tilghman (2010)
10.1016/j.jbiomech.2004.06.027 / J. Biomech. / Traction in smooth muscle cells varies with cell spreading. by Tolić–Nørrelykke (2005)
10.1152/ajpcell.00169.2002 / Am. J. Physiol., Cell Physiol. / Spatial and temporal traction response in human airway smooth muscle cells. by Tolić–Nørrelykke (2002)
10.1158/0008-5472.CAN-08-4859 / Cancer Res. / The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells. by Ulrich (2009)
10.1002/cm.10037 / Cell Motil. Cytoskeleton / Micropatterning tractional forces in living cells. by Wang (2002)
10.1038/nrm2592 / Nat. Rev. Mol. Cell Biol. / Mechanotransduction in development: a growing role for contractility. by Wozniak (2009)
10.1083/jcb.200305010 / J. Cell Biol. / ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. by Wozniak (2003)

Dates

Type	When
Created	12 years, 10 months ago (Oct. 24, 2012, 11:54 p.m.)
Deposited	3 years, 9 months ago (Nov. 12, 2021, 11:26 a.m.)
Indexed	5 days, 7 hours ago (Aug. 27, 2025, 11:44 a.m.)
Issued	12 years, 8 months ago (Dec. 15, 2012)
Published	12 years, 8 months ago (Dec. 15, 2012)
Published Print	12 years, 8 months ago (Dec. 15, 2012)

Funders 0

None

BibTeX

@article{Mih_2012, title={Matrix stiffness reverses the effect of actomyosin tension on cell proliferation}, volume={125}, ISSN={0021-9533}, url={http://dx.doi.org/10.1242/jcs.108886}, DOI={10.1242/jcs.108886}, number={24}, journal={Journal of Cell Science}, publisher={The Company of Biologists}, author={Mih, Justin D. and Marinkovic, Aleksandar and Liu, Fei and Sharif, Asma S. and Tschumperlin, Daniel J.}, year={2012}, month=dec, pages={5974–5983} }

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      "article-title": "Growth control by intracellular tension and extracellular stiffness.",
      "volume": "18",
      "author": "Assoian",
      "year": "2008",
      "journal-title": "Trends Cell Biol."
    },
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      "doi-asserted-by": "publisher",
      "first-page": "466",
      "DOI": "10.1038/35074532",
      "article-title": "Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates.",
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      "author": "Balaban",
      "year": "2001",
      "journal-title": "Nat. Cell Biol."
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      "first-page": "108",
      "DOI": "10.1038/nrc2544",
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      "year": "2009",
      "journal-title": "Nat. Rev. Cancer"
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      "first-page": "C595",
      "DOI": "10.1152/ajpcell.00270.2001",
      "article-title": "Traction fields, moments, and strain energy that cells exert on their surroundings.",
      "volume": "282",
      "author": "Butler",
      "year": "2002",
      "journal-title": "Am. J. Physiol. Cell Physiol."
    },
    {
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      "doi-asserted-by": "publisher",
      "first-page": "3907",
      "DOI": "10.1529/biophysj.106.084806",
      "article-title": "Nonmuscle myosin IIA-dependent force inhibits cell spreading and drives F-actin flow.",
      "volume": "91",
      "author": "Cai",
      "year": "2006",
      "journal-title": "Biophys. J."
    },
    {
      "key": "2021111216264738500_b7",
      "doi-asserted-by": "publisher",
      "first-page": "68",
      "DOI": "10.1007/s12195-010-0102-6",
      "article-title": "Substrate stiffness and cell area predict cellular traction stresses in single cells and cells in contact.",
      "volume": "3",
      "author": "Califano",
      "year": "2010",
      "journal-title": "Cell Mol. Bioeng."
    },
    {
      "key": "2021111216264738500_b8",
      "doi-asserted-by": "publisher",
      "first-page": "1425",
      "DOI": "10.1126/science.276.5317.1425",
      "article-title": "Geometric control of cell life and death.",
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      "author": "Chen",
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      "journal-title": "Science"
    },
    {
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      "doi-asserted-by": "publisher",
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      "author": "Chicurel",
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      "volume": "9",
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      "article-title": "The mechanism of action of cantharidin in smooth muscle.",
      "volume": "123",
      "author": "Knapp",
      "year": "1998",
      "journal-title": "Br. J. Pharmacol."
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      "volume": "102",
      "author": "Kong",
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      "volume": "303",
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