Single Molecule Force Measurements in Living Cells Reveal a Minimally Tensioned Integrin State

Alice C. Chang, Armen H. Mekhdjian, Masatoshi Morimatsu, Aleksandra Kirillovna Denisin, Beth L. Pruitt, Alexander R. Dunn

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Integrins mediate cell adhesion to the extracellular matrix and enable the construction of complex, multicellular organisms, yet fundamental aspects of integrin-based adhesion remain poorly understood. Notably, the magnitude of the mechanical load experienced by individual integrins within living cells is unclear, due principally to limitations inherent to existing techniques. Here we use Förster resonance energy transfer-based molecular tension sensors to directly measure the distribution of loads experienced by individual integrins in living cells. We find that a large fraction of integrins bear modest loads of 1-3 pN, while subpopulations bearing higher loads are enriched within adhesions. Further, our data indicate that integrin engagement with the fibronectin synergy site, a secondary binding site specifically for α5β1 integrin, leads to increased levels of α5β1 integrin recruitment to adhesions but not to an increase in overall cellular traction generation. The presence of the synergy site does, however, increase cells’ resistance to detachment by externally applied loads. We suggest that a substantial population of integrins experiencing loads well below their peak capacities can provide cells and tissues with mechanical integrity in the presence of widely varying mechanical loads.

Original languageEnglish
Pages (from-to)10745-10752
Number of pages8
JournalACS Nano
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 27 2016

Keywords

  • cell adhesion
  • integrin
  • mechanobiology
  • single molecule
  • tension sensor

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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    Chang, A. C., Mekhdjian, A. H., Morimatsu, M., Denisin, A. K., Pruitt, B. L., & Dunn, A. R. (2016). Single Molecule Force Measurements in Living Cells Reveal a Minimally Tensioned Integrin State. ACS Nano, 10(12), 10745-10752. https://doi.org/10.1021/acsnano.6b03314