SUBSTRATUM TOPOGRAPHY EFFECTS ON CORNEAL EPITHELIUM

描述：基底膜具有许多特征，这些特征极大地影响 细胞功能，包括特定蛋白质和功能团，一个储存库 生长因子和其他营养因子，以及一个复杂的三维 贴壁细胞将突起延伸到其中， 形成粘附斑。 底层的三维地形 底物，独立于特定的受体-配体相互作用，已经被 最近被证明会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尺度（>1um）的影响。 细胞行为的特征。 这些“大规模”研究与 由于PI的实验室已经显示， 前角膜上皮下面的基底膜， 复杂的三维纳米级（> 1 μ m特征尺寸）结构， 扩大其表面积，用于细胞膜相互作用约。 3500-4000 折 本提案的总体目的是调查 基底膜的非尺度（<1微米）地形特征 前角膜上皮细胞行为的基础。 在这 应用，提出了一种多层次的方法来测试3个假设 使用细胞生物学中的体外方法和最新的纳米级技术 制造技术。 假设1：基底的仿生非尺度地形特征 膜调节基本细胞行为。 假设2：完全合成的表面可以用特征进行工程化 （颠簸与毛孔与纤维）的尺寸、分布和表面 化学物质，将调节细胞行为的方式类似于 “天然”基底膜的拓扑结构。 假设3. 非尺度地形调节细胞对其他细胞的反应， 众所周知的细胞活性化合物。

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.