Force-induced focal adhesion translocation: effects of force amplitude and frequency

Vascular endothelial cells rapidly transduce local mechanical forces into biological signals through numerous processes including the activation of focal adhesion sites. To examine the mechanosensing capabilities of these adhesion sites, focal adhesion translocation was monitored over the course of...

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Published inAmerican Journal of Physiology: Cell Physiology Vol. 56; no. 4; pp. C954 - C962
Main Authors MACK, P. J, KAAZEMPUR-MOFRAD, M. R, KARCHER, H, LEE, R. T, KAMM, R. D
Format Journal Article
LanguageEnglish
Published Bethesda, MD American Physiological Society 01.10.2004
Subjects
Biochemistry
Biological and medical sciences
Cell interactions, adhesion
Cell physiology
Cells
Circulatory system
Fundamental and applied biological sciences. Psychology
Molecular and cellular biology
Signal transduction
Tyrosine
Endothelial cell
Load
Genistein
viscoelastic model
Activation
Src tyrosine kinase
Adhesion
Cell surface
Apical membrane
Signal transduction
Integrin
paxillin
Mechanotransduction
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Summary:Vascular endothelial cells rapidly transduce local mechanical forces into biological signals through numerous processes including the activation of focal adhesion sites. To examine the mechanosensing capabilities of these adhesion sites, focal adhesion translocation was monitored over the course of 5 min with GFP-paxillin while applying nN-level magnetic trap shear forces to the cell apex via integrin-linked magnetic beads. A nongraded steady-load threshold for mechanotransduction was established between 0.90 and 1.45 nN. Activation was greatest near the point of forcing (<7.5 micro m), indicating that shear forces imposed on the apical cell membrane transmit nonuniformly to the basal cell surface and that focal adhesion sites may function as individual mechanosensors responding to local levels of force. Results from a continuum, viscoelastic finite element model of magnetocytometry that represented experimental focal adhesion attachments provided support for a nonuniform force transmission to basal surface focal adhesion sites. To further understand the role of force transmission on focal adhesion activation and dynamics, sinusoidally varying forces were applied at 0.1, 1.0, 10, and 50 Hz with a 1.45 nN offset and a 2.25 nN maximum. At 10 and 50 Hz, focal adhesion activation did not vary with spatial location, as observed for steady loading, whereas the response was minimized at 1.0 Hz. Furthermore, applying the tyrosine kinase inhibitors genistein and PP2, a specific Src family kinase inhibitor, showed tyrosine kinase signaling has a role in force-induced translocation. These results highlight the mutual importance of force transmission and biochemical signaling in focal adhesion mechanotransduction. [PUBLICATION ABSTRACT]
ISSN:0363-6143
1522-1563