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Biophys J. 2008 Dec;95(11):5424-31. doi: 10.1529/biophysj.108.139584. Epub 2008 Aug 8.

Cooperativity in adhesion cluster formation during initial cell adhesion.

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Department of New Materials and Biosystems, Max-Planck-Institute for Metals Research, Stuttgart, Germany.


We have studied the initial phase of cell adhesion as a function of the lateral organization of individual integrin molecules with single-cell force microscopy. Nanostructures, consisting of hexagonally ordered gold dots, were prepared with diblock-copolymer micelle lithography and functionalized with arginine- glycine-aspartate peptides, thus defining integrin position with nanometer resolution. Adhesion strength was characterized with an atomic force microscope and both cell detachment forces and work of detachment showed a reinforcement of adhesion if the distance between integrin molecules was <70 nm. This reinforcement had already occurred at cell-substrate contact times <5 min. We believe our results show quantitatively the relevance of the distance between adjacent integrin binding sites rather than their density. Furthermore, we propose a model describing the cooperative stabilization of early integrin clusters as a function of receptor patterning at the nanoscale.

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