SURFACE INFLUENCES ON CELL SIGNALING AND PROLIFERATION

描述：申请人提出使用基于整合分子的 一种研究生物材料表面化学对细胞影响的方法 与组织工程相关的信号传导和增殖途径， 生物材料发展 研究的长期目标是 将特定的细胞生物学和遗传反应联系起来， 具体地，申请人将首先测试分子生物学的假设， 生物材料表面化学的水平控制对 细胞跨膜信号传导事件。 使用一系列经过充分研究的有机 自组装薄膜组件，他们将试图解释观察 在这些不同的表面上培养的细胞表现出一定的表面 化学依赖性生长和附着模式。 实验 针对信号激活蛋白磷酸化和粘着斑。 第二，申请人将研究整合素介导的调节， 局部接触，应力纤维和随后的通路的形成 细胞增殖的遗传调控。 第三，申请人将使用 已经用组成型活性或 组成型失活Rho突变体，然后将评估 细胞附着，形成局部接触和应力纤维，并调节生长 在各种表面上的特定基因，例如c-myc、creb、c-fos和c-jun。 基因工程方法将用于检测细胞的终点， 信号级联反应的各种表面。 申请人声称， 这种方法将使细胞反应的生物测定的发展成为可能 到生物材料，这两种材料的内在能力的诊断 以支持细胞生长，并将提供信息，这是基本的， 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.