title: Single Molecule Force Measurements in Living Cells Reveal a Minimally Tensioned Integrin State.
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 α5β1integrin, leads to increased levels of α5β1integrin 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.
authors: Alice C
authors: AC
authors: Chang
authors: Armen H
authors: AH
authors: Mekhdjian
authors: Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University , Okayama 700-0082, Japan.
authors: Masatoshi
authors: M
authors: Morimatsu
authors: Aleksandra Kirillovna
authors: AK
authors: Denisin
authors: Stanford Cardiovascular Institute, Stanford University , 265 Campus Drive, Stanford, California 94305, United States.|Department of Molecular and Cellular Physiology, Stanford University School of Medicine , Stanford, California 94305, United States.
authors: Beth L
authors: BL
authors: Pruitt
authors: Stanford Cardiovascular Institute, Stanford University , 265 Campus Drive, Stanford, California 94305, United States.
authors: Alexander R
authors: AR
authors: Dunn
mesh_terms: D002448:Cell Adhesion; D005109:Extracellular Matrix; D005353:Fibronectins; D006801:Humans; D039081:Integrin alpha5beta1 / Q000502:physiology; D016023:Integrins / Q000502:physiology*; D055595:Mechanical Phenomena
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D016023:Integrins
keywords: cell adhesion; integrin; mechanobiology; single molecule; tension sensor