MICROFABRICATED SUBSTRATA FOR CARDIAC MECHANOBIOLOGY

描述（来自申请人摘要的逐字）：机械因素，例如 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类似生命的细胞培养系统。履行党章赋予的监督执纪问 生物工程研究资助计划（PAR-99-009），我们是AR 一个由生物工程师、分子心脏病学家、肌肉专家 细胞生物学家和化学家本建议的总体目标是 建立一种新的细胞培养体系，研究心肌细胞重塑的过程， 在体外维持分化的体内细胞表型。我们的团队已被 工作了两年，拟议的文化系统，创造了 微加工技术与表面化学的结合，现在更加紧密， 模拟体内心脏生理学。 目标1。改变生物膜的表面微形貌， 附着、形状、密度、每个DNA的总蛋白质以及肌球蛋白与总蛋白质的比例 比率。 目标二。为了改变表面化学性质并测量粘附依赖性细胞 信号和增长。 目标3。为了使附着在化学键上的心脏细胞机械变形， 目的1和2中制备的显微织构表面，并研究其形态、生长 和基因表达。 我们希望这种新的模型培养系统将允许心脏适应性的研究。 和病理生理过程，而不需要 整个动物的后遗症改变心输出量。这是至关重要的一步， 通往心脏器官形成和心脏组织工程的道路。这些 基质也可用于其他细胞类型机械生物学研究 已知对负荷有反应，例如骨、结缔组织、内皮细胞， 平滑肌和骨骼肌。

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.