Surface chemistry modulates fibronectin conformation and directs integrin binding and specificity to control cell adhesion

Journal of Biomedical Materials Research - Part A - Tập 66A Số 2 - Trang 247-259 - 2003
Benjamin G. Keselowsky1,2, David M. Collard3, Andrés J. Garcı́a2,4
1Coulter School of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332
2Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332
3School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332
4Woodruff School of Mechanical Engineering, 315 Ferst Drive, Room 2314 IBB, Georgia Institute of Technology, Atlanta, Georgia 30332

Tóm tắt

AbstractIntegrin‐mediated cell adhesion to proteins adsorbed onto synthetic surfaces anchors cells and triggers signals that direct cell function. In the case of fibronectin (Fn), adsorption onto substrates of varying properties alters its conformation/structure and its ability to support cell adhesion. In the present study, self‐assembled monolayers (SAMs) of alkanethiols on gold were used as model surfaces to investigate the effects of surface chemistry on Fn adsorption, integrin binding, and cell adhesion. SAMs presenting terminal CH3, OH, COOH, and NH2 functionalities modulated adsorbed Fn conformation as determined through differences in the binding affinities of monoclonal antibodies raised against the central cell‐binding domain (OH > COOH = NH2 > CH3). Binding of α5β1 integrin to adsorbed Fn was controlled by SAM surface chemistry in a manner consistent with antibody binding (OH > COOH = NH2 > CH3), whereas αV integrin binding followed the trend: COOH >> OH = NH2 = CH3, demonstrating α5β1 integrin specificity for Fn adsorbed onto the NH2 and OH SAMs. Cell adhesion strength to Fn‐coated SAMs correlated with α5β1 integrin binding (OH > COOH = NH2 > CH3), and experiments with function‐perturbing antibodies demonstrated that this receptor provides the dominant adhesion mechanism in this cell model. This work establishes an experimental framework to analyze adhesive mechanisms controlling cell‐surface interactions and provides a general strategy of surface‐directed control of adsorbed protein activity to manipulate cell function in biomaterial and biotechnological applications. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 66A: 247–259, 2003

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Journal of Biomedical Materials Research - Part A

Tập 66A Số 2

247-259

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