Several features of basement membranes profoundly influence cell function, including the presence of specific proteins, functional groups, growth factors, and other trophic agents, as well as a complex 3 dimensional topography into which adherent cells extend processes and form plaques. The 3 dimensional topography of the basement membrane, independent of specific receptor-ligand interactions, has been shown recently to influence multiple fundamental cell behaviors. The majority of studies conducted to date have evaluated the effect of large scale (> 1 mu/M) features of surface topography on cell behavior. The relevance of these """"""""large-scale"""""""" studies to cell behavior in vivo is not clear, since our laboratories have shown that the surface of basement membranes, including the basement membrane underlying urothelial cells, actually consists of a complex 3-dimensional nanoscale (< 1 mu/M feature size) architecture that dramatically amplifies its surface area for cell-basement membrane interaction. The overall purpose of this proposal is to determine the consequences of nanoscale topographic features on urothelial cell behavior. In this application, a multi-disciplinary approach is proposed, employing techniques in cell biology and state of the art methods of nanofabrication, to test the following hypothesis: 1. Totally synthetic surfaces can be engineered through controlled fabrication with biologically relevant feature types, dimensions and distributions that will modulate urothelial cell behaviors. The proposed studies will generate information pertinent to tissue engineering and development of prosthetic devices for use in the urinary tract, as well as providing data to initiate mechanistic studies.
