SUBSTRATUM TOPOGRAPHY EFFECTS ON CORNEAL EPITHELIUM

描述：基底膜有许多特性，这些特性对 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 贴壁细胞延伸到的突起和细胞延伸到的拓扑图 形成粘连斑块。下垫面的三维地形 底物，独立于特定的受体-配体相互作用，一直是 最近发现会影响基本的细胞行为。大多数人 到目前为止进行的研究已经评估了大规模(&gt；1um)的效果 关于细胞行为的特征。这些“大规模”研究与 由于PI的实验室表明，细胞在体内的行为尚不清楚 角膜前上皮下的基底膜由 复杂的3维纳米级(1微米特征大小)体系结构 扩大其表面积约为细胞-膜相互作用。3500-4000 收牌。这项建议的总体目的是调查影响 基底膜的非尺度(1微米)地形特征 角膜前上皮下的细胞行为。在这 应用，提出了一种多学科方法来检验3个假说 体外方法在细胞生物学和纳米技术中的应用 制造技术。 假设1：基底的仿生非尺度地形特征 膜调节细胞的基本行为。 假设2：完全合成的表面可以用特征来设计 (凹凸VS毛孔VS纤维)大小、分布和表面可控 一种化学，它将以类似于 “天然”基底膜的形态。 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.