Cell shape provides global control of focal adhesion assembly.
Cell spreading was controlled independently of the amount and density of immobilized integrin ligand by culturing cells on single adhesive islands of different sizes (100-2500 microm(2)) and shapes (squares, circles, and lines) or on many smaller (3-5 microm diameter) circular islands that were coated with a saturating density of fibronectin and separated by non-adhesive regions. The amount of focal adhesions (FAs) containing vinculin and phosphotyrosine increased in direct proportion to cell spreading under all conditions. FAs localized asymmetrically along the periphery of the small islands that experienced highest tensional stress, and FA staining increased when cytoskeletal tension was stimulated with thrombin, whereas inhibitors of contractility promoted FA disassembly. Thus, these findings demonstrate the existence of an "inside-out" mechanism whereby global cell distortion produces increases in cytoskeletal tension that feed back to drive local changes in FA assembly. This complex interplay between cell morphology, mechanics, and adhesion may be critical to how cells integrate from and function in living tissues.
Chen
Christopher S
CS
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 2120, USA.
Alonso
Jose L
JL
Ostuni
Emanuele
E
Whitesides
George M
GM
Ingber
Donald E
DE
D000199:Actins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology*; D018929:Cell Culture Techniques; D048429:Cell Size; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism; D022001:Focal Adhesions / Q000737:chemistry / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D013314:Stress, Mechanical; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D005353:Fibronectins; D016023:Integrins; D016596:Vinculin