The integrin expression profile modulates orientation and dynamics of force transmission at cell-matrix adhesions

Hayri E. Balcioglu*, Hedde van Hoorn, Dominique M. Donato, Thomas Schmidt, Erik H.J. Danen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

73 Citations (Scopus)

Abstract

Integrin adhesion receptors connect the extracellular matrix (ECM) to the cytoskeleton and serve as bidirectional mechanotransducers. During development, angiogenesis, wound healing and cancer progression, the relative abundance of fibronectin receptors, including integrins α5ß1 and αvß3, changes, thus altering the integrin composition of cell-matrix adhesions. Here, we show that enhanced αvß3 expression can fully compensate for loss of α5ß1 and other ß1 integrins to support outside-in and inside-out force transmission. α5ß1 and αvß3 each mediate actin cytoskeletal remodeling in response to stiffening or cyclic stretching of the ECM. Likewise, α5ß1 and αvß3 support cellular traction forces of comparable magnitudes and similarly increase these forces in response to ECM stiffening. However, cells using αvß3 respond to lower stiffness ranges, reorganize their actin cytoskeleton more substantially in response to stretch, and show more randomly oriented traction forces. Centripetal traction force orientation requires long stress fibers that are formed through the action of Rho kinase (ROCK) and myosin II, and that are supported by α5ß1. Thus, altering the relative abundance of fibronectin-binding integrins in cell-matrix adhesions affects the spatiotemporal organization of force transmission.

Original languageEnglish
Pages (from-to)1316-1326
Number of pages11
JournalJournal of Cell Science
Volume128
Issue number7
DOIs
Publication statusPublished - 1 Apr 2015
Externally publishedYes

Bibliographical note

Funding:
Support for this work came from the Netherlands Organization for Scientific
Research NWO-FOM [grant numbers 09MMC03 to H.E.B. and 09MMC01 to H.v.H.
and D.M.D.]; and from the Dutch Cancer Society [grant number UL 2010-4670].


Publisher Copyright:
© 2015. Published by The Company of Biologists Ltd.

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