CAREER: Hybrid Surfaces to Control Cell Adhesion and Function

0093226 Garcia该提案的研究和教育活动侧重于细胞受体-配体相互作用和表面工程，以控制粘附受体的结合和细胞扩散，从而指导细胞功能。 细胞与细胞外基质的粘附主要由粘附受体的整合素家族介导。 除了锚定细胞，整合素提供调节细胞功能的信号。 由于细胞粘附在细胞功能中的核心作用，细胞粘附在许多生物技术和生物医学应用中至关重要，包括体外培养系统，生物材料和组织工程。本项目的总体研究目标是设计受纤维连接蛋白（一种重要的和普遍存在的细胞外基质蛋白）启发的生物粘附表面，以指导细胞功能。 具体而言，合成的微图案化表面将被工程化以呈现纤连蛋白的特定结构域，其结合特定的整合素并控制细胞扩散。 细胞粘附到这些工程表面将分析整合素结合，粘附强度，细胞内信号传导，和粘着斑组装。 然后将检查特定整合素结合和细胞铺展对成骨细胞（骨形成细胞）分化的影响。 通过对粘附相互作用的机理分析，该项目将为生物活性表面的合理设计提供更深入的细胞功能和新的生物分子策略的理解。该项目的教育部分侧重于开发基于Web的交互式软件模块，以模拟受体-配体相互作用。 模拟模块将开发中学科学课程，以说明受体配体相互作用的基本概念，使用高度动画图形界面。 另一个建模平台将为研究生水平的细胞工程课程开发，为深入研究受体-配体相互作用提供图形界面，包括参数分析，时间依赖性模拟和实验数据分析。 这些教学工具允许将研究整合到教育体验中，并允许在传统实验室环境中不可能进行的虚拟实验。 最后，这些单元的网络格式便于广泛传播和推广。

0093226GarciaThe 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.