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Biophys J. 2018 Oct 16;115(8):1569-1579. doi: 10.1016/j.bpj.2018.08.045. Epub 2018 Sep 10.

Local Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale.

Author information

1
Department of Medicine (Cardiology) and Yale Cardiovascular Research Center, Yale University, New Haven, Connecticut.
2
Bioinformatics and Structural Biology Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California.
3
Bioinformatics and Structural Biology Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California. Electronic address: dorit@sbpdiscovery.org.
4
Department of Medicine (Cardiology) and Yale Cardiovascular Research Center, Yale University, New Haven, Connecticut; Departments of Cell Biology and Biomedical Engineering, Yale University, New Haven, Connecticut. Electronic address: martin.schwartz@yale.edu.

Abstract

Cellular force transmission and mechanotransduction are critical in embryogenesis, normal physiology, and many diseases. Talin plays a key role in these processes by linking integrins to force-generating actomyosin. Using the previously characterized FRET-based talin tension sensor, we observed variations of tension both between and within individual focal adhesions in the same cell. Assembling and sliding adhesions showed gradients with higher talin tension toward the cell center, whereas mature, stable adhesions had uniform talin tension. Total talin accumulation was maximal in high-tension regions; by contrast, vinculin intensity was flat or maximal at the adhesion center, and actin intensity was maximal toward the cell center. To investigate mechanism, we combined talin tension imaging with cellular cryotomography to visualize the correlated actin organization at nanometer resolution. Regions of high talin tension had highly aligned linear actin filaments, whereas regions of low tension had less-well-aligned F-actin. These results reveal an orchestrated spatiotemporal relationship between talin tension, actin/vinculin localization, local actin organization, and focal adhesion dynamics.

PMID:
30274833
PMCID:
PMC6372196
[Available on 2019-10-16]
DOI:
10.1016/j.bpj.2018.08.045

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