title: Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts.
abstract: Fibroblast migration involves complex mechanical interactions with the underlying substrate. Although tight substrate contact at focal adhesions has been studied for decades, the role of focal adhesions in force transduction remains unclear. To address this question, we have mapped traction stress generated by fibroblasts expressing green fluorescent protein (GFP)-zyxin. Surprisingly, the overall distribution of focal adhesions only partially resembles the distribution of traction stress. In addition, detailed analysis reveals that the faint, small adhesions near the leading edge transmit strong propulsive tractions, whereas large, bright, mature focal adhesions exert weaker forces. This inverse relationship is unique to the leading edge of motile cells, and is not observed in the trailing edge or in stationary cells. Furthermore, time-lapse analysis indicates that traction forces decrease soon after the appearance of focal adhesions, whereas the size and zyxin concentration increase. As focal adhesions mature, changes in structure, protein content, or phosphorylation may cause the focal adhesion to change its function from the transmission of strong propulsive forces, to a passive anchorage device for maintaining a spread cell morphology.
authors.affiliation: Department of Physiology, University of Massachusetts Medical School, 377 Plantation Street, Worcester, MA 01605, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Beningo
authors.forename: M
authors.initials: M
authors.lastname: Dembo
authors.forename: I
authors.initials: I
authors.lastname: Kaverina
authors.forename: J V
authors.initials: JV
authors.lastname: Small
authors.forename: Y L
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology*; D006054:Goldfish; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D009010:Monte Carlo Method; D011554:Pseudopodia / Q000502:physiology; D013314:Stress, Mechanical; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D000205:Actomyosin