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Vol. 12, Issue 12, 3947-3954, December 2001

Distinct Roles of Frontal and Rear Cell-Substrate Adhesions in Fibroblast Migration

Steven Munevar,^* Yu-li Wang,^* and Micah Dembo

 ^*Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605; and  Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215

Cell migration involves complex physical and chemical interactions with the substrate. To probe the mechanical interactions under different regions of migrating 3T3 fibroblasts, we have disrupted cell-substrate adhesions by local application of the GRGDTP peptide, while imaging stress distribution on the substrate with traction force microscopy. Both spontaneous and GRGDTP-induced detachment of the trailing edge caused extensive cell shortening, without changing the overall level of traction forces or the direction of migration. In contrast, disruption of frontal adhesions caused dramatic, global loss of traction forces before any significant shortening of the cell. Although traction forces and cell migration recovered within 10-20 min of transient frontal treatment, persistent treatment with GRGDTP caused the cell to develop traction forces elsewhere and reorient toward a new direction. We conclude that contractile forces of a fibroblast are transmitted to the substrate through two distinct types of adhesions. Leading edge adhesions are unique in their ability to transmit active propulsive forces. Their functions cannot be transferred directly to existing adhesions upon detachment. Trailing end adhesions create passive resistance during cell migration and readily redistribute their loads upon detachment. Our results indicate the distinct nature of mechanical interactions at the leading versus trailing edges, which together generate the mechanical interactions for fibroblast migration.

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Online version of this article contains video material for certain figures. Online version available at www.molbiolcell.org.

Corresponding author. E-mail address: yuli.wang{at}umassmed.edu.

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Molecular Biology of the Cell
Vol. 12, 3947-3954, December 2001
Copyright © 2001 by The American Society for Cell Biology

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