Title

Cell locomotion and focal adhesions are regulated by substrate flexibility

UMMS Affiliation

Department of Physiology

Date

2-12-1998

Document Type

Article

Subjects

3T3 Cells; Acrylic Resins; Animals; Arsenicals; Biomechanics; Cell Adhesion; Cell Line; Cell Movement; Collagen; Enzyme Inhibitors; Extracellular Matrix; Mice; Myosins; Phosphotyrosine; Protein Tyrosine Phosphatases; Rats; Surface Properties; Vinculin

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661-5.

Related Resources

Link to Article in PubMed

Journal Title

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

PubMed ID

9391082