Corneal epithelial cells rest upon a basement membrane, which represents a unique specialization of the extracellular matrix. Basement membranes have many features that greatly influence cell function including a complex three-dimensional topography. 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 (> 1 um) features on cell behavior. The relevance of these """"""""large-scale"""""""" studies to cell behavior in vivo is not clear since our laboratories have shown the basement membrane underlying the anterior corneal epithelium to consist of a complex 3-dimensional nanoscale (< 1 micron feature size) architecture which amplifies its surface area for cell-membrane interaction. Additionally, we have shown that corneal epithelial cells respond differently to these large-scale features than to much finer nanoscale features that are more representative of the topographic features encountered in vivo. The overall purpose of this proposal is to investigate the ability of nanoscale (< 1 micron) topographic features to modulate fundamental cell behaviors. In this application, a multi-disciplinary approach is proposed to test 3 hypotheses using in vitro methodologies in cell biology and state-of-the-art nanoscale fabrication techniques. Hypothesis 1: Totally synthetic surfaces can be engineered through controlled fabrication with biologically relevant feature types (bumps vs. pores vs. fibers), dimensions and distributions that will modulate corneal epithelial cell behaviors. Hypothesis 2: Biomimetic nanoscale topographic features of the basement membrane modulate fundamental corneal cell behaviors. Hypothesis 3: Cytoactive compounds interact with Nanoscale topography to modulate corneal epithelial cell behavior.
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