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PNAS 102 (17): 5953-5957

Copyright © 2005 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / APPLIED BIOLOGICAL SCIENCES

Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation

Benjamin G. Keselowsky*,{dagger}, David M. Collard{ddagger}, and Andrés J. García*,{dagger},§

*Woodruff School of Mechanical Engineering, {dagger}Petit Institute for Bioengineering and Bioscience, and {ddagger}School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332

Received for publication October 4, 2004.

Abstract: Biomaterial surface chemistry has profound consequences on cellular and host responses, but the underlying molecular mechanisms remain poorly understood. Using self-assembled monolayers as model biomaterial surfaces presenting well defined chemistries, we demonstrate that surface chemistry modulates osteoblastic differentiation and matrix mineralization independently from alterations in cell proliferation. Surfaces were precoated with equal densities of fibronectin (FN), and surface chemistry modulated FN structure to alter integrin adhesion receptor binding. OH- and NH2-terminated surfaces up-regulated osteoblast-specific gene expression, alkaline phosphatase enzymatic activity, and matrix mineralization compared with surfaces presenting COOH and CH3 groups. These surface chemistry-dependent differences in cell differentiation were controlled by binding of specific integrins to adsorbed FN. Function-perturbing antibodies against the central cell binding domain of FN completely inhibited matrix mineralization. Furthermore, blocking antibodies against β1 integrin inhibited matrix mineralization on the OH and NH2 surfaces, whereas function-perturbing antibodies specific for β3 integrin increased mineralization on the COOH substrate. These results establish surface-dependent differences in integrin binding as a mechanism regulating differential cellular responses to biomaterial surfaces. This mechanism could be exploited to engineer materials that control integrin binding specificity to elicit desired cellular activities to enhance the integration of biomaterials and improve the performance of biotechnological culture supports.

Key Words: cell adhesion • signaling • osteoblast • mineralization


§ To whom correspondence should be addressed at: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Room 2314 IBB, Atlanta, GA 30332-0363. E-mail: andres.garcia{at}me.gatech.edu.

Edited by Sheldon Weinbaum, City College of the City University of New York, New York, NY, and approved March 17, 2005

Author contributions: D.M.C. and A.J.G. designed research; B.G.K. performed research; D.M.C. contributed new reagents/analytic tools; B.G.K. and A.J.G. analyzed data; and B.G.K. and A.J.G. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: ALP, alkaline phosphatase; FTIR, Fourier transform infrared; FN, fibronectin; SAM, self-assembled monolayer.

© 2005 by The National Academy of Sciences of the USA


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