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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064956-03
Application #
6637530
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Lundberg, Martha
Project Start
2001-03-01
Project End
2005-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2003
Total Cost
$468,054
Indirect Cost
Name
University of Illinois at Chicago
Department
Physiology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
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Senyo, Samuel E; Koshman, Yevgeniya E; Russell, Brenda (2007) Stimulus interval, rate and direction differentially regulate phosphorylation for mechanotransduction in neonatal cardiac myocytes. FEBS Lett 581:4241-7
Boateng, Samuel Y; Belin, Rashad J; Geenen, David L et al. (2007) Cardiac dysfunction and heart failure are associated with abnormalities in the subcellular distribution and amounts of oligomeric muscle LIM protein. Am J Physiol Heart Circ Physiol 292:H259-69
Qi, Lixin; Boateng, Samuel Y (2006) The circadian protein Clock localizes to the sarcomeric Z-disk and is a sensor of myofilament cross-bridge activity in cardiac myocytes. Biochem Biophys Res Commun 351:1054-9
Yu, Ji-Guo; Russell, Brenda (2005) Cardiomyocyte remodeling and sarcomere addition after uniaxial static strain in vitro. J Histochem Cytochem 53:839-44
Boateng, Samuel Y; Lateef, Syed S; Mosley, William et al. (2005) RGD and YIGSR synthetic peptides facilitate cellular adhesion identical to that of laminin and fibronectin but alter the physiology of neonatal cardiac myocytes. Am J Physiol Cell Physiol 288:C30-8
Norman, James J; Desai, Tejal A (2005) Control of cellular organization in three dimensions using a microfabricated polydimethylsiloxane-collagen composite tissue scaffold. Tissue Eng 11:378-86
Crot, Carrie A; Wu, Chunping; Schlossman, Mark L et al. (2005) Determining the conformation of an adsorbed Br-PEG-peptide by long period X-ray standing wave fluorescence. Langmuir 21:7899-906
Vracar-Grabar, Marina; Russell, Brenda (2004) Creatine kinase is an alpha myosin heavy chain 3'UTR mRNA binding protein. J Muscle Res Cell Motil 25:397-404
Edirisinghe, Praneeth D; Lateef, Syed S; Crot, Carrie A et al. (2004) Derivatization of surface-bound peptides for mass spectrometric detection via threshold single photon ionization. Anal Chem 76:4267-70

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