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Unformatted text preview: Free energy landscape of receptor-mediated cell adhesion Tianyi Yang Department of Physics, The University of Texas at Austin, Austin, Texas 78712 Muhammad H. Zaman a ! Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712 and Institute of Theoretical Chemistry, The University of Texas at Austin, Austin, Texas 78712 s Received 13 September 2006; accepted 1 December 2006; published online 30 January 2007 d Receptor-mediated cell adhesion plays a critical role in cell migration, proliferation, signaling, and survival. A number of diseases, including cancer, show a strong correlation between integrin activation and metastasis. A better understanding of cell adhesion is highly desirable for not only therapeutic but also a number of tissue engineering applications. While a number of computational models and experimental studies have addressed the issue of cell adhesion to surfaces, no model or theory has adequately addressed cell adhesion at the molecular level. In this paper, the authors present a thermodynamic model that addresses receptor-mediated cell adhesion at the molecular level. By incorporating the entropic, conformational, solvation, and long- and short-range interactive components of receptors and the extracellular matrix molecules, they are able to predict adhesive free energy as a function of a number of key variables such as surface coverage, interaction distance, molecule size, and solvent conditions. Their method allows them to compute the free energy of adhesion in a multicomponent system where they can simultaneously study adhesion receptors and ligands of different sizes, chemical identities, and conformational properties. The authors’ results not only provide a fundamental understanding of adhesion at the molecular level but also suggest possible strategies for designing novel biomaterials. © 2007 American Institute of Physics . f DOI: 10.1063/1.2424985 g I. INTRODUCTION Cell surface receptors, such as integrins, mediate cell- matrix adhesion and play a central role in a number of physi- ological scenarios, ranging from mechanotransduction to cell migration. 1 , 2 These processes are necessary for proper cell function, survival, and proliferation. Upregulation of inte- grins has also been associated with increased invasion rates in a number of cancers. 2 Cell-matrix adhesion is also the focus of a number of areas in biotechnology such as drug delivery, tissue engineering, and stem-cell therapy. 3 Since the discovery of integrins in the 1980s, there has been a signifi- cant effort to understand and modulate cell adhesion. 4 While most of these efforts have been purely experimental in na- ture, a number of theoretical efforts have also advanced our understanding of cell adhesion and the mechanochemical as- pects of integrin-surface contact....
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This note was uploaded on 07/25/2011 for the course EMA 6580 taught by Professor Staff during the Spring '08 term at University of Florida.
- Spring '08