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，佐治亚州技术凝集素介导的细胞粘附研究所对细胞外基质的粘附进行调节，调节众多组织的组织，维持和修复，并且粘合性相互作用的异常通常与病理状态有关。 此外，与合成材料的细胞粘合剂相互作用控制了宿主对生物医学设备的反应，组织工程结构的生物融合以及生物技术细胞培养支持的发展。 粘合剂过程包括整合素受体与其细胞外配体，整合素聚类的结合以及包含细胞骨架和信号分子的离散超分子结构的组装。这些局灶性粘附复合物充当了细胞及其细胞外环境之间的结构联系和信号转导元件。尽管在调节粘附的破译生化途径中取得了重大进展，但细胞与其环境之间的机械相互作用仍然很熟悉。该项目的目的是分析纳米级局灶性粘附几何结构（群集数，大小，间距）对细胞粘附力和焦点粘附信号的影响。假设焦点粘附的几何组织根据“接触分裂”原理调节粘附力。 “接触式分裂”的力学解释了比与均等接触区域的一个接触相比，有多少小接触能产生更高的粘附力。 粘合剂界面的结构将使用聚集的纳米图案粘合剂岛和多价配体的各种构型调节，以改变整联蛋白聚类和焦点粘附区域和间距。 整联蛋白结合和局灶性粘附组件和成纤维细胞中的信号传导将使用生化和免疫染色技术进行定量，并将使用我们的流体动力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测定方法，纳米图案方法和独特的细胞生物学试剂，以精确操纵焦点复杂组织和生物分子结构，以分析这些粘合剂如何产生粘合力。 这些研究将对纳米级组织和结构对粘合力的产生和调节的贡献进行严格的综合分析。 这些研究将对细胞及其细胞外基质之间机械相互作用的调节产生新的了解。本项目还将导致基于多学科的，综合的观点的独特分析技能的本科和研究生研究人员的高级培训。 佐治亚理工学院或我们的亚特兰大大学中心（AUC）倡议的一名人数不足的少数族裔学生每年都将在该项目中招募，以鼓励高级教育和科学和工程学的未来职业。 AUC是世界上最大的非裔美国人私立学校高等教育财团，包括克拉克·亚特兰大大学，莫尔豪斯学院和斯佩尔曼学院。