Nanostructure in Cell Adhesive Forces

生态旅游- 0827719 a。整合素介导的细胞对细胞外基质的粘附调节着许多组织的组织、维持和修复，而粘附相互作用的异常通常与病理状态有关。此外，细胞粘附与合成材料的相互作用决定了宿主对生物医学设备的反应，组织工程构建的生物整合，以及生物技术细胞培养支持的发展。粘附过程包括整合素受体与细胞外配体结合，整合素聚集，以及包含细胞骨架和信号分子的离散超分子结构的组装。这些黏附复合物在细胞和细胞外环境之间起着结构联系和信号转导元件的作用。虽然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。本项目的目的是分析纳米尺度黏附几何结构（簇数、大小、间距）对细胞黏附力和黏附信号的影响。假设黏着点的几何组织根据“接触分裂”原理调节黏着力。“接触分裂”力学解释了在相同的接触面积下，许多小的接触可以产生比一个接触更高的附着力。粘合界面的结构将通过不同配置的纳米簇状粘合岛和多价配体来调节，以改变整合素的聚集和焦点粘合面积和间距。将使用生化和免疫染色技术量化成纤维细胞中的整合素结合和局灶粘附组装和信号传导，并使用我们的流体动力旋转盘试验分析粘附强度。拟议的研究将整合强大的定量分析，纳米图谱方法和独特的细胞生物学试剂，以精确地操纵焦点复杂组织和生物分子结构，以分析这些粘附复合物如何产生粘附力。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提供严格的、综合的分析。这些研究将对细胞及其细胞外基质之间的机械相互作用的调节产生新的理解。该项目还将为本科生和研究生研究人员提供基于多学科综合视角的独特分析技能的高级培训。每年将从佐治亚理工学院或我们的亚特兰大大学中心（AUC）计划中招募一名未被充分代表的少数族裔学生参与该项目，以鼓励在科学和工程领域接受高等教育和未来的职业发展。AUC是世界上最大的非裔美国人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。

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.