Force-induced destabilization of focal adhesions at defined integrin spacings on nanostructured surfaces.
Focal adhesions are the anchoring points of cells to surfaces and are responsible for a large number of surface sensing processes. Nanopatterning studies have shown physiological changes in fibroblasts as a result of decreasing density of external binding ligands. The most striking of these changes is a decreased ability to form mature focal adhesions when lateral ligand distances exceed 76 nm. These changes are usually examined in the context of protein signaling and protein interactions. We show a physical explanation based on the balance between the forces acting on individual ligand connections and the reaction kinetics of those ligands. We propose three stability regimes for focal adhesions as a function of ligand spacing and applied stress: a stable regime, an unstable regime in which a large fraction of unbound protein causes adhesion disintegration, and a regime in which the applied force is too high to form an adhesion structure.
de Beer
Alex G F
AG
Department of New Materials and Biosystems, Max Planck Institute for Metals Research, Heisenbergstrasse 3, D70569 Stuttgart, Germany. debeer@mf.mpg.de
Cavalcanti-Adam
E Ada
EA
Majer
Günter
G
Lopez-García
M
M
Kessler
H
H
Spatz
Joachim P
JP
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry; D022001:Focal Adhesions / Q000737:chemistry*; D016023:Integrins / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D025941:Protein Interaction Mapping; D051381:Rats; D015398:Signal Transduction
D005353:Fibronectins; D016023:Integrins; D008024:Ligands; D008823:Micelles