Basement Membrane Topography and Urothelial Function

描述（由申请人提供）：基底膜的几个特征深刻地影响细胞功能，包括特定蛋白质、功能基团、生长因子和其他营养因子的存在，以及贴壁细胞延伸过程并形成斑块的复杂三维地形。独立于特定受体-配体相互作用的基底膜的三维形貌最近被证明影响多种基本细胞行为。迄今为止进行的大多数研究都评估了大尺度（bbb101mu /M）表面形貌特征对细胞行为的影响。这些“大规模”研究与体内细胞行为的相关性尚不清楚，因为我们的实验室已经表明，基底膜的表面，包括尿路上皮细胞下的基底膜，实际上由一个复杂的三维纳米尺度（< 1 mu/M特征尺寸）结构组成，该结构极大地扩大了细胞-基底膜相互作用的表面积。该建议的总体目的是确定纳米级地形特征对尿路上皮细胞行为的影响。在本应用中，提出了一种多学科的方法，采用细胞生物学技术和纳米制造的最新方法，来检验以下假设：完全合成的表面可以通过控制制造来设计，具有生物学相关的特征类型，尺寸和分布，将调节尿路上皮细胞的行为。拟议的研究将产生与组织工程和用于泌尿道的假体装置开发相关的信息，并为启动机制研究提供数据。

DESCRIPTION (provided by applicant): 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.