CAREER: Hybrid Surfaces to Control Cell Adhesion and Function

这项建议的研究和教育活动集中在细胞受体-配体的相互作用和表面工程，以控制黏附受体的结合和细胞的扩散，以指导细胞功能。细胞与细胞外基质的黏附主要由黏附受体的整合素家族介导。除了锚定细胞外，整合素还提供调节细胞功能的信号。由于细胞黏附在细胞功能中的核心作用，细胞黏附在许多生物技术和生物医学应用中是至关重要的，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在纤维连接蛋白的启发下设计生物黏附表面，引导细胞功能。具体地说，合成的微图案表面将被设计成呈现纤维连接蛋白的特定结构域，这些结构域与特定的整合素结合并控制细胞扩散。细胞对这些工程化表面的黏附将从整合素结合、黏附强度、细胞内信号和焦点黏附组装等方面进行分析。然后将检测特定整合素结合和细胞扩散对成骨细胞(骨形成细胞)分化的影响。通过对粘附剂相互作用的机理分析，本项目将为合理设计生物活性表面提供对细胞功能和新的生物分子策略的更深入的了解。本项目的教学内容侧重于开发基于Web的交互式软件模块来模拟受体-配体相互作用。将为中学科学课程开发模拟模块，以使用高度动画的图形界面来说明受体-配体相互作用的基本概念。将为研究生水平的细胞工程课程开发另一个建模平台，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、时间相关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，并允许进行在传统实验室环境中不可能实现的虚拟实验。最后，这些单元的基于网络的格式允许广泛传播和推广。

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.