CAREER: Hybrid Surfaces to Control Cell Adhesion and Function

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

0093226 Garcia The research and education activities of this proposal focus on cellular receptor-ligand interactions and the engineering of surfaces to control the binding of adhesion receptors and cell spreading to direct cell function. Cell adhesion to extracellular matrices is primarily mediated by the integrin family of adhesion receptors. In addition to anchoring cells, integrins provide signals that regulate cell function. Due to its central role in cell function, cell adhesion is crucial to many biotechnological and biomedical applications, including in vitro culture systems, biomaterials and tissue engineering. The overall research objective of this project is to engineer bioadhesive surfaces inspired by fibronectin, an essential and ubiquitous extracellular matrix protein, to direct cell function. Specifically, synthetic micropatterned surfaces will be engineered to present specific domains of fibronectin that bind to particular integrins and control cell spreading. Cell adhesion to these engineered surfaces will be analyzed in terms of integrin binding, adhesion strength, intracellular signaling, and focal adhesion assembly. The effects of specific integrin binding and cell spreading on the differentiation of osteoblasts, bone-forming cells, will then be examined. By focusing on a mechanistic analysis of adhesive interactions, this project will provide a deeper understanding of cell function and novel biomolecular strategies for the rational design of bioactive surfaces. The educational component of this project focuses on the development of interactive Web-based software modules to model receptor-ligand interactions. Simulation modules will be developed for middle school science courses to illustrate fundamental concepts of receptor-ligand interactions using highly animated graphical interfaces. Another modeling platform will be developed for a graduate-level cellular engineering course to provide a graphical interface for the in depth examination of receptor-ligand interactions, including parametric analysis, time-dependent simulations, and analysis of experimental data. These instructional tools allow for the integration of research into the educational experience and permit virtual experimentation that is not possible in conventional laboratory settings. Finally, the Web-based format of these modules allows for wide spread dissemination and outreach.