MICROFABRICATED SUBSTRATA FOR CARDIAC MECHANOBIOLOGY

点击翻译按钮获取中文摘要

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.