DOI: 10.1073/pnas.94.25.13661. Cell locomotion and focal adhesions are regulated by substrate flexibility

Cell locomotion and focal adhesions are regulated by substrate flexibility

10.1073/pnas.94.25.13661

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Responses of cells to mechanical properties of the adhesion substrate were examined by culturing normal rat kidney epithelial and 3T3 fibroblastic cells on a collagen-coated polyacrylamide substrate that allows the flexibility to be varied while maintaining a constant chemical environment. Compared with cells on rigid substrates, those on flexible substrates showed reduced spreading and increased rates of motility or lamellipodial activity. Microinjection of fluorescent vinculin indicated that focal adhesions on flexible substrates were irregularly shaped and highly dynamic whereas those on firm substrates had a normal morphology and were much more stable. Cells on flexible substrates also contained a reduced amount of phosphotyrosine at adhesion sites. Treatment of these cells with phenylarsine oxide, a tyrosine phosphatase inhibitor, induced the formation of normal, stable focal adhesions similar to those on firm substrates. Conversely, treatment of cells on firm substrates with myosin inhibitors 2,3-butanedione monoxime or KT5926 caused the reduction of both vinculin and phosphotyrosine at adhesion sites. These results demonstrate the ability of cells to survey the mechanical properties of their surrounding environment and suggest the possible involvement of both protein tyrosine phosphorylation and myosin-generated cortical forces in this process. Such response to physical parameters likely represents an important mechanism of cellular interaction with the surrounding environment within a complex organism.

Bibliography

Pelham, R. J., & Wang, Y. (1997). Cell locomotion and focal adhesions are regulated by substrateâflexibility. Proceedings of the National Academy of Sciences, 94(25), 13661â13665.

Authors 2

Robert J. Pelham (first)
Yu-li Wang (additional)

References 35 Referenced 2,588

10.1083/jcb.120.3.577
10.1097/00001622-199401000-00015
10.1016/S0955-0674(96)80051-2
10.1038/385537a0
10.1126/science.7684161
10.1242/jcs.104.3.613
10.1083/jcb.133.6.1403
10.1126/science.7846531
10.1083/jcb.131.3.791
10.1002/jcp.1041630121
10.1152/physrev.1995.75.3.519
10.1016/S0092-8674(00)81856-5
10.1016/0014-4827(73)90579-X
10.1038/273345a0
10.1083/jcb.109.1.317
10.1016/0003-2697(81)90057-9
N M McKenna, Y-l Wang Methods Cell Biol 29, 105–205 (1989). / Methods Cell Biol by McKenna N M (1989)
J W Goding Monoclonal Antibodies: Practice and Principals (Academic, New York), pp. 75–77 (1983). / Monoclonal Antibodies: Practice and Principals by Goding J W (1983)
A V Heuvelen Physics: A General Introduction (Little, Brown, New York), pp. 299 (1982). / Physics: A General Introduction by Heuvelen A V (1982)
10.1083/jcb.127.6.1957
10.1083/jcb.104.6.1521
10.1083/jcb.102.4.1430
10.1242/jcs.109.5.981
10.1016/S0955-0674(96)80059-7
10.1083/jcb.119.4.893
P A Maher, E B Pasquale, J Y J Wang, S J Singer Proc Natl Acad Sci USA 82, 6570–6580 (1985). / Proc Natl Acad Sci USA by Maher P A (1985)
10.1073/pnas.90.23.11177
S Nakanishi, K Yamada, K Iwanashi, K Kuroda, K Kase Mol Pharmacol 37, 482–488 (1990). / Mol Pharmacol by Nakanishi S (1990)
10.1093/oxfordjournals.jbchem.a122717
10.1126/science.6987736
10.1038/385450a0
10.1146/annurev.cb.01.110185.001331
10.1006/excr.1995.1361
10.1126/science.276.5317.1425
10.1016/S0074-7696(08)61986-5

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:55 p.m.)
Indexed	14 hours, 9 minutes ago (Sept. 1, 2025, 6:32 a.m.)
Issued	27 years, 8 months ago (Dec. 9, 1997)
Published	27 years, 8 months ago (Dec. 9, 1997)
Published Online	27 years, 8 months ago (Dec. 9, 1997)
Published Print	27 years, 8 months ago (Dec. 9, 1997)

Funders 0

None

BibTeX

@article{Pelham_1997, title={Cell locomotion and focal adhesions are regulated by substrate flexibility}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.25.13661}, DOI={10.1073/pnas.94.25.13661}, number={25}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Pelham, Robert J. and Wang, Yu-li}, year={1997}, month=dec, pages={13661–13665} }

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