Munevar, StevenWang, Yu-LiDembo, Micah2022-08-232022-08-232001-12-122008-11-24<p>Munevar S, Wang YL, Dembo M. Distinct roles of frontal and rear cell-substrate adhesions in fibroblast migration. Mol Biol Cell. 2001 Dec;12(12):3947-54. doi: 10.1091/mbc.12.12.3947. PMID: 11739792; PMCID: PMC60767.</p>1059-1524 (Print)10.1091/mbc.12.12.394711739792https://hdl.handle.net/20.500.14038/34229Cell 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.en-USCopyright the authors. Publisher PDF posted as allowed by the publisher's author right policy at https://www.molbiolcell.org/info-for-authors#license. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e., the appearance of the edited manuscript in an online issue of MBoC), the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons Attribution 4.0 International (CC-BY 4.0) License (https://creativecommons.org/licenses/by/4.0).http://creativecommons.org/licenses/by/4.0/Journal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1885&amp;context=gsbs_sp&amp;unstamped=1https://escholarship.umassmed.edu/gsbs_sp/886671449gsbs_sp/886