SUBSTRATUM TOPOGRAPHY EFFECTS ON CORNEAL EPITHELIUM

基质地形对角膜上皮的影响

• 批准号: 2678467
• 负责人: CHRISTOPHER John MURPHY
• 金额: $ 20.61万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2678467
• 关键词: artificial membranes; atomic force microscopy; basement membrane; bioassay; cell adhesion; cell biology; cell cell interaction; cell differentiation; cell migration; cell proliferation; corneal epithelium; epidermal growth factor; human tissue; insulinlike growth factor; membrane activity; membrane reconstitution /synthesis; membrane structure; norepinephrine; scanning electron microscopy; simian virus 40; substance P

DESCRIPTION: Basement membranes have many features which greatly influence cell function including specific proteins and functional groups, a reservoir of growth factors and other trophic agents, and a complex three-dimensional topography into which adherent cells extend processes and to which cells form adhesion plaques. The three dimensional topography of the underlying substrate, independent of specific receptor-ligand interactions, has been recently shown to influence fundamental cell behaviors. The majority of studies conducted to date have evaluated the effect of large scale (>1um) features on cell behavior. The relevance of these "large scale" studies to cell behavior in vivo is not clear since the PI's laboratories have shown the basement membrane underlying the anterior corneal epithelium to consist of a complex 3-dimensional nanoscale (>1um feature size) architecture which amplifies its surface area for cell-membrane interaction approx. 3500-4000 fold. The overall purpose of this proposal is to investigate the influence of nonoscale (<1micron) topographic features of the basement membrane underlying the anterior corneal epithelium on cell behavior. In this application, a multi-displinary approach is proposed to test 3 hypotheses using in vitro methodologies in cell biology and state of the art nanoscale fabrication techniques. Hypothesis 1: Biomimetic nonoscale topographic features of the basement membrane modulate fundamental cell behaviors. Hypothesis 2: Totally synthetic surfaces can be engineered with features (bumps v.s. pores v.s. fibers) of controlled size, distribution and surface chemistry that will modulate cell behaviors in a fashion similar to the topography of the "native" basement membrane. Hypothesis 3. Nonoscale topography modulates the response of cells to other well known cytoactive compounds.

描述： 基底膜具有许多特征，这些特征极大地影响 细胞功能包括特定的蛋白质和功能基团，一个储存库 生长因子和其他营养剂，以及复杂的三维 贴壁细胞延伸过程的拓扑结构以及细胞的拓扑结构 形成粘附斑块。 底层的三维地形 底物，独立于特定的受体-配体相互作用，已被 最近被证明可以影响基本的细胞行为。 大多数 迄今为止进行的研究已经评估了大规模（>1um）的影响 细胞行为的特征。 这些“大规模”研究的相关性 细胞在体内的行为尚不清楚，因为 PI 的实验室已经表明 前角膜上皮下面的基底膜由 复杂的 3 维纳米级（>1um 特征尺寸）架构 扩大其细胞膜相互作用的表面积约。 3500-4000 折叠。 本提案的总体目的是调查影响 基底膜的非尺度（<1微米）形貌特征 前角膜上皮细胞行为的基础。 在这个 应用程序中，提出了一种多学科方法来检验 3 个假设 使用细胞生物学的体外方法和最先进的纳米尺度 制造技术。 假设1：仿生地下室的非尺度地形特征 膜调节基本的细胞行为。 假设 2：全合成表面可以设计具有特征 （凸块、孔隙、纤维）的尺寸、分布和表面受控 化学物质将以类似于 “天然”基底膜的地形。 假设 3. 非尺度拓扑调节细胞对其他物质的反应 众所周知的细胞活性化合物。