
@article {25251,
	title = {Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	year = {2017},
	month = {2017 Oct 03},
	pages = {10648-10653},
	abstract = {<p>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.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1701136114},
	author = {Swaminathan, Vinay and Kalappurakkal, Joseph Mathew and Mehta, Shalin B and Nordenfelt, Pontus and Moore, Travis I and Koga, Nobuyasu and Baker, David A and Oldenbourg, Rudolf and Tani, Tomomi and Mayor, Satyajit and Springer, Timothy A and Waterman, Clare M}
}
@article {28246,
	title = {Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration.},
	journal = {Nat Commun},
	volume = {8},
	year = {2017},
	month = {2017 Dec 11},
	pages = {2047},
	abstract = {<p>Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy. Cytoskeleton and ligand-bound integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. Our results place atomic, {\r A}-scale structures of cell surface receptors in the context of functional and cellular, μm-scale measurements.</p>
},
	issn = {2041-1723},
	doi = {10.1038/s41467-017-01848-y},
	author = {Nordenfelt, Pontus and Moore, Travis I and Mehta, Shalin B and Kalappurakkal, Joseph Mathew and Swaminathan, Vinay and Koga, Nobuyasu and Lambert, Talley J and Baker, David and Waters, Jennifer C and Oldenbourg, Rudolf and Tani, Tomomi and Mayor, Satyajit and Waterman, Clare M and Springer, Timothy A}
}
