SUBSTRATUM TOPOGRAPHY EFFECTS ON CORNEAL EPITHELIUM

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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.