MICROFABRICATED SUBSTRATA FOR CARDIAC MECHANOBIOLOGY

描述(逐字摘自申请者摘要)：机械因素，如 力和细胞附着，已知参与维持 心肌细胞。不幸的是，心脏机械生物学研究受到阻碍。 因为我们还没有一个逼真的细胞培养系统。的要求。 生物工程研究资助计划(PAR-99-009)，我们是 由生物工程师、分子心脏病专家、肌肉专家组成的跨学科团队 细胞生物学家和化学家。这项提议的总体目标是 建立一种新的细胞培养体系研究心肌细胞重塑过程 体外培养，保持体内分化的细胞表型。我们队有 工作了两年，拟议的文化体系，由 微制造技术与表面化学相结合，现在更紧密地结合在一起， 模拟活体心脏生理学。 目的1.改变生物膜表面微形貌并测定细胞 附着、形状、密度、每个DNA的总蛋白以及肌球蛋白与总蛋白的比例 比率。 目的2.改变表面化学并测定黏附依赖细胞 信号和增长。 目的3.使附着在化学键上的心肌细胞机械变形， 在AIMS 1和AIMS 2中制备的微织构表面及其形貌、生长研究 和基因表达。 我们希望这种新的模型培养系统将使心脏适应性研究成为可能。 和体外病理生理过程，没有引入的复杂性 整个动物对心输出量的改变。这是关键的一步 心脏器官发生和心脏组织工程的途径。这些 底物也可用于其他类型细胞的机械生物学研究。 已知对负荷有反应，如骨、结缔组织、内皮细胞、 平滑的和骨骼肌。

DESCRIPTION (Verbatim from Applicant's Abstract): Mechanical factors, such as force and cell attachment, are known to be involved in the maintenance of the cardiac myocyte. Unfortunately, cardiac mechano-biological research is hampered because we do not yet have a life-like cell culture system. As required by the Bioengineering Research Grant initiative (PAR-99-009), we are ar interdisciplinary team of a bioengineer, a molecular cardiologist, a muscle cell biologist and a chemist. The overall objective of this proposal is to develop a new cell culture system to study the process of myocyte remodeling in vitro which maintains a differentiated in vivo cell phenotype. Our team has worked for two years and the proposed culture system, created by microfabrication technology coupled with surface chemistry, now more closely, mimics in vivo heart physiology. Aim 1. To alter the surface microtopography of biomembranes and determine cell attachment, shape, density, total protein per DNA, and myosin to total protein ratios. Aim 2. To alter the surface chemistry and measure adhesion-dependent cell signaling and growth. Aim 3. To mechanically deform cardiac cells attached on chemically-bonded, microtextured surfaces prepared in aims 1 and 2 and to study morphology, growth and gene expression. We expect this novel model culture system will allow study of cardiac adaptive and patho-physiological processe in vitro without the complexity introduced by whole animal sequella to altered cardiac output. This is an essential step in the path towards heart organogenesis and cardiac tissue engineering. These substrata wil1 also be useful for study of mechanobiology of other cell types known to respond to load, such as bone, connective tissues, endothelia cells, smooth and skeletal muscle.