SURFACE INFLUENCES ON CELL SIGNALING AND PROLIFERATION

描述：申请者建议使用集成的基于分子的 生物材料表面化学对细胞影响的研究方法 与组织工程相关的信号和增殖途径 生物材料开发。这项研究的长远目标是 将特定的细胞生物学和遗传反应联系起来，这些反应对 具体地说，申请者将首先测试分子 生物材料表面化学的水平控制对 细胞跨膜信号事件。使用经过充分研究的有机阵列 自组装的薄膜组件，他们将试图解释观察到的 在这些不同的表面上培养的细胞表现出一定的表面 依赖化学物质的成长和依恋模式。实验是 针对信号激活蛋白的磷酸化和局部粘连。 其次，申请者将调查整合素介导的调控 焦点接触、应力纤维和随后的路径的形成 细胞增殖的基因调控。第三，申请者将使用 已被组分活性基因或基因重组基因 构成不活跃的Rho突变体，然后将评估 细胞附着，形成焦点接触，应力纤维和调节生长 C-myc、CREB、c-fos、c-jun等不同表面的特异性基因。 然后将使用基因工程方法来分析细胞的终点 信号响应不同的表面而级联。申请者声称 这一方法将使细胞反应的生物测定得以发展。 对生物材料来说，这既是对材料内在能力的诊断 以支持细胞生长，并将提供基本的信息 了解细胞对生物材料的反应。

DESCRIPTION: The applicants propose to use an integrated molecular based approach to study the influence of biomaterial surface chemistry on cell signaling and proliferation pathways relevant to tissue engineering and biomaterials development. The long term objective of the studies is to correlate specific cell biology and genetic responses which are important to Specifically, the applicants will first test the hypothesis that molecular level control of biomaterial surface chemistry has a profound impact upon cell transmembrane signaling events. Using a well studied array of organic self assembled film components, they will attempt to explain the observation that cells cultured on these various surfaces exhibit certain surface chemistry-dependent growth and attachment patterns. Experiments are directed at signal-activated protein phosphorylation and focal adhesions. Secondly, the applicants will investigate integrin mediated regulation of the formation of focal contacts, stress fibers and subsequent pathways for genetic regulation of cell proliferation. Thirdly, the applicants will use cells which have been transfected with either constitutively active or constitutively inactive Rho mutants, and will then assess the ability of cells to attach, form focal contacts and stress fibers and regulate growth specific genes such as c-myc, creb, c-fos, and c-jun on various surfaces. Genetic engineering methods will then be used to assay the endpoint of cell signaling cascade in response to various surfaces. The applicants claim this approach will enable the development of bioassays of cellular responses to biomaterials that are both diagnostic of a material's intrinsic ability to support cell growth and will provide information which is fundamental to understanding the responses of cells to biomaterials.