GSBS Student Publications

Title

Regulation of mechanical interactions between fibroblasts and the substratum by stretch-activated Ca2+ entry

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Physiology

Date

11-25-2003

Document Type

Article

Medical Subject Headings

Animals; Calcium; Calcium Channels; Cell Adhesion; Cell Movement; Fibroblasts; Focal Adhesions; Gadolinium; Mice; Microscopy, Fluorescence; NIH 3T3 Cells; Pseudopodia; Vinculin

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Ca2+ ions have long been implicated in regulating various aspects of cell movements. We found that stretching forces applied through flexible substrata induced increases in both intracellular Ca2+ concentration and traction forces of NIH3T3 fibroblasts. Conversely, application of gadolinium, an inhibitor of stretch-activated ion channels, or removal of extracellular free Ca2+ caused inhibition of traction forces. Gadolinium treatment also inhibited cell migration without affecting the spread morphology or protrusive activities. Local application of gadolinium to the trailing region had no detectable effect on the overall traction forces, while local application to the leading edge caused a global inhibition of traction forces and cell migration, suggesting that stretch-activated channels function primarily at the leading edge. Immunofluorescence microscopy indicated that gadolinium caused a pronounced decrease in vinculin and phosphotyrosine concentrations at focal adhesions. Our observations suggest that stretch-activated Ca2+ entry in the frontal region regulates the organization of focal adhesions and the output of mechanical forces. This mechanism probably plays an important role in sustaining cell migration and in mediating active and passive responses to mechanical signals.

Rights and Permissions

Citation: J Cell Sci. 2004 Jan 1;117(Pt 1):85-92. Epub 2003 Nov 19. Link to article on publisher's site

DOI of Published Version

10.1242/jcs.00795

Related Resources

Link to article in PubMed

Journal Title

Journal of cell science

PubMed ID

14627625