The objectives of this program are to investigate the biomechanical behavior of red blood cells, white blood cells, endothelial cells, smooth muscle cells and other components of the vasculature; to study the micromechanics and molecular basis of cell-cell interactions; and to assess the roles of these cell properties in microcirculatory regulation in health and disease. The rheological properties of normal and abnormal blood cells, endothelial cells and smooth muscle cells will be studied by micromechanical techniques. The experimental results will be subjected to computational analysis and serve as the basis of theoretical modeling. These findings will be correlated with the molecular organization of the cell membrane, especially the membrane proteins. The Program will employ a multidisciplinary, systematic approach involving parallel experimental and theoretical investigations, which cover the spectrum ranging from molecular biology tot he microcirculation. Experiments will be conducted to study the effects of experimental manipulations of the molecular characteristics of the cell membrane on (a) the biomechanical properties of the cells and (b) the micromechanical and molecular energetics of their interactions (neutrophil-neutrophil, leukocyte-endothelial, erythrocyte-macrophage, etc.) The effects of alterations of blood cell properties on flow dynamics will be studied in the microcirculation; particular emphasis will be placed on WBC kinetics and the attendant changes in circulatory functions. The coordinated effort is aimed at elucidating the molecular basis and physiological roles of the biomechanical behavior of red blood cells, white blood cells, endothelial cells and vascular smooth muscle cells, with the ultimate goal of providing the fundamental knowledge needed to improve diagnosis and treatment of cardiovascular and blood diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL043026-04
Application #
3098767
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1990-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Dewan, Sukriti; McCabe, Kimberly J; Regnier, Michael et al. (2016) Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study. J Phys Chem B 120:8264-75
Yao, Weijuan; Chu, Xin; Sung, Lanping Amy (2015) Cell type-restricted expression of erythrocyte tropomodulin Isoform41 in exon 1 knockout/LacZ knock-in heterozygous mice. Gene Expr Patterns 17:45-55
Sche, Paul; Vera, Carlos; Sung, L Amy (2011) Intertwined ** spectrin meeting helical actin protofilament in the erythrocyte membrane skeleton: wrap-around vs. point-attachment. Ann Biomed Eng 39:1984-93
de Oliveira, Mauricio; Vera, Carlos; Valdez, Pierre et al. (2010) Nanomechanics of multiple units in the erythrocyte membrane skeletal network. Ann Biomed Eng 38:2956-67
Yao, Weijuan; Sung, Lanping Amy (2010) Erythrocyte tropomodulin isoforms with and without the N-terminal actin-binding domain. J Biol Chem 285:31408-17
Su, Susan S; Schmid-Schönbein, Geert W (2010) Internalization of Formyl Peptide Receptor in Leukocytes Subject to Fluid Stresses. Cell Mol Bioeng 3:20-29
Yao, Weijuan; Sung, Lanping Amy (2009) Specific expression of E-Tmod (Tmod1) in horizontal cells: implications in neuronal cell mechanics and glaucomatous retina. Mol Cell Biomech 6:71-82
Schmid-Schönbein, Geert W (2009) 2008 Landis Award lecture. Inflammation and the autodigestion hypothesis. Microcirculation 16:289-306
Chien, Shu (2008) Effects of disturbed flow on endothelial cells. Ann Biomed Eng 36:554-62
Jacot, Jeffrey G; McCulloch, Andrew D; Omens, Jeffrey H (2008) Substrate stiffness affects the functional maturation of neonatal rat ventricular myocytes. Biophys J 95:3479-87

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