Nanostructure in Cell Adhesive Forces

细胞粘附力中的纳米结构

• 批准号: 0827719
• 负责人: Andres Garcia
• 金额: --
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0827719&HistoricalAwards=false
• 关键词: Nanostructure; Cell; Adhesive; Forces

CBET-0827719A. Garcia, Georgia Institute of TechnologyIntegrin-mediated cell adhesion to extracellular matrices regulates the organization, maintenance and repair of numerous tissues, and abnormalities in adhesive interactions are often associated with pathological states. Moreover, cell adhesive interactions with synthetic materials govern host responses to biomedical devices, biological integration of tissue-engineered constructs, and development of biotechnological cell culture supports. The adhesive process comprises integrin receptor binding to their extracellular ligand, integrin clustering, and assembly of discrete supramolecular structures containing cytoskeletal and signaling molecules. These focal adhesion complexes function as structural links and signal transduction elements between the cell and its extracellular environment. While significant progress has been attained in deciphering biochemical pathways regulating adhesion, the mechanical interactions between a cell and its environment remain poorly understood. The objective of this project is to analyze the effects of nanoscale focal adhesion geometrical structure (cluster number, size, spacing) on cell adhesive force and focal adhesion signaling. It is hypothesized that the geometrical organization of the focal adhesion modulates adhesive force based on the "contact splitting" principle. "Contact splitting" mechanics explains how many small contacts can produce a higher adhesion force than one contact with equal contact area. The architecture of the adhesive interface will be modulated using various configurations of clustered nanopatterned adhesive islands and multi-valent ligands to alter integrin clustering and focal adhesion area and spacing. Integrin binding and focal adhesion assembly and signaling in fibroblasts will be quantified using biochemical and immunostaining techniques, and adhesion strength will be analyzed using our hydrodynamic spinning disk assay. The proposed research will integrate robust quantitative assays, nanopatterning approaches, and unique cell biology reagents to precisely manipulate focal complex organization and biomolecular structure in order to analyze how these adhesive complexes generate adhesive forces. These studies will provide rigorous, integrated analyses of the contributions of nanoscale organization and structure to the generation and regulation of adhesive forces. These studies will generate a new understanding of the regulation of mechanical interactions between a cell and its extracellular matrix.This project will also result in the advanced training of undergraduate and graduate researchers with unique analytical skills based on a multi-disciplinary, integrative perspective. One underrepresented minority student, either from Georgia Tech or our Atlanta University Center (AUC) Initiative, will be recruited every year to work in this project to encourage advanced education and future careers in science and engineering. The AUC is the world's largest consortium of African American private institutions of higher education, including Clark Atlanta University, Morehouse College, and Spelman College.

CBET-0827719A。加西亚，佐治亚理工学院整合素介导的细胞粘附到细胞外基质调节许多组织的组织、维护和修复，粘附相互作用的异常通常与病理状态相关。 此外，细胞粘附与合成材料的相互作用控制着宿主对生物医学设备的反应、组织工程结构的生物整合以及生物技术细胞培养支持物的开发。 粘附过程包括整合素受体与其胞外配体结合、整合素聚类以及含有细胞骨架和信号分子的离散超分子结构的组装。这些粘着斑复合物充当细胞与其细胞外环境之间的结构连接和信号转导元件。尽管在破译调节粘附的生化途径方面取得了重大进展，但细胞与其环境之间的机械相互作用仍然知之甚少。该项目的目的是分析纳米级粘附斑几何结构（簇数、大小、间距）对细胞粘附力和粘附斑信号传导的影响。据推测，粘着斑的几何组织基于“接触分裂”原理调节粘合力。 “触点分裂”机制解释了有多少个小触点可以比具有相同接触面积的一个触点产生更高的粘附力。 将使用簇状纳米图案粘合剂岛和多价配体的各种配置来调节粘合剂界面的结构，以改变整合素簇和焦点粘附面积和间距。 将使用生化和免疫染色技术对成纤维细胞中的整合素结合、粘着斑组装和信号传导进行量化，并使用我们的流体动力学旋转盘测定法对粘附强度进行分析。拟议的研究将整合强大的定量分析、纳米图案化方法和独特的细胞生物学试剂，以精确操纵焦点复合物组织和生物分子结构，从而分析这些粘合复合物如何产生粘合力。 这些研究将对纳米级组织和结构对粘附力的产生和调节的贡献提供严格的综合分析。 这些研究将对细胞与其细胞外基质之间的机械相互作用的调节产生新的理解。该项目还将基于多学科、综合的视角，对具有独特分析技能的本科生和研究生研究人员进行高级培训。 每年都会招募一名来自佐治亚理工学院或亚特兰大大学中心 (AUC) 计划的少数族裔学生参与该项目，以鼓励高等教育和未来在科学和工程领域的职业生涯。 AUC 是世界上最大的非裔美国私立高等教育机构联盟，包括克拉克亚特兰大大学、莫尔豪斯学院和斯佩尔曼学院。