Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions

Research output: Contribution to journalArticle


Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven “retrograde flow” of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues.


  • Vinay Swaminathan
  • Joseph Mathew Kalappurakkal
  • Shalin B. Mehta
  • Pontus Nordenfelt
  • Travis I. Moore
  • Nobuyasu Koga
  • David A. Baker
  • Rudolf Oldenbourg
  • Tomomi Tani
  • Satyajit Mayor
  • Timothy A. Springer
  • Clare M. Waterman
External organisations
  • Marine Biological Laboratory
  • National Heart Lung and Blood Institute
  • National Centre for Biological Sciences
  • Boston Children's Hospital
  • University of Washington
  • Harvard University
  • Institute for Molecular Science
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology


  • Cell migration, Fluorescence polarization microscopy, Mechanosensing
Original languageEnglish
Pages (from-to)10648-10653
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number40
StatePublished - 2017 Oct 3