28. A NOVEL ROLE FOR VINCULIN IN MYOCARDIAL FIBER MECHANICS

Department: Bioengineering
Faculty Advisor(s): Jeffrey Omens | Andrew McCulloch

Primary Student
Name: Jared Rylan Tangney
Email: jtangney@ucsd.edu
Phone: 858-534-6616
Grad Year: 2012

Abstract
Vinculin has been previously shown to play a significant role in mechanotransduction and may affect myocardial mechanical function in a directionally-dependent manner. Cardiac MRI tagging in a vinculin knockout (VclKO) mouse model revealed significant decreases in systolic sheet-normal shear strain (P<0.05) and systolic sheet strain (P<0.05) in KO mice compared with littermate wildtype (WT) controls. We hypothesized that an increase in transverse systolic stress development may explain these observations, and changes in myofilament lattice spacing in the VclKO could alter systolic stress in the myocytes. Actin-myosin lattice spacing was then measured and normalized to sarcomere length in barium-contracted WT and VclKO hearts with values of 19.11.51 nm and 21.81.39 nm, respectively. These results were used as inputs in a structural model of crossbridge geometry similar to that of Schoenberg (1980), which showed a significant increase in the radial component of sacromere force in the VclKO compared with WT. The calculated distribution of forces was then used in a three-dimensional finite element model in which end systolic sheet strains were predicted. The results matched the trends seen experimentally between the WT and VclKO mice. These results suggest that the change in systolic strains seen experimentally in the VclKO mice can be explained by the increase in lattice spacing seen in the knockout mice.

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