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：地下室膜具有许多极大影响的功能 细胞功能，包括特定蛋白质和官能团，储层 生长因子和其他营养剂，以及复杂的三维 地形上，粘附细胞扩展了过程以及细胞的延伸 形成粘附斑。 底层的三维形状 与特定受体配体相互作用无关的底物已经是 最近证明会影响基本细胞行为。 大多数 迄今为止进行的研究已经评估了大规模的影响（> 1UM） 细胞行为的特征。 这些“大规模”研究与 由于PI的实验室已显示，体内的细胞行为尚不清楚 前角膜上皮的基础膜构成 一个复杂的三维纳米级（> 1UM特征大小）体系结构的体系结构 扩增其表面积以进行细胞膜相互作用。 3500-4000 折叠。 该提案的总体目的是调查影响 地下室膜的非oscale（<1micron）地形特征 在细胞行为的前角膜上皮下面的基础。 在这个 应用，提出了一种多层次方法来检验3个假设 在细胞生物学和最先进的纳米级中使用体外方法论 制造技术。 假设1：地下室的仿生非oscale非oscale地形特征 膜调节基本细胞行为。 假设2：完全合成的表面可以用特征设计 （颠簸V.S.毛孔V.S.纤维）受控尺寸，分布和表面 化学反应将以类似于类似的方式调节细胞行为 “本地”地下室膜的地形。 假设3。非oscale地形调节细胞对其他的反应 众所周知的细胞活性化合物。