One of the main reasons for heart failure due to hypertension is that the structure of the heart tissue changes with time, altering its mechanical capabilities. The heart tissue is mainly made of two "materials": cells (called myocytes) and fibers (specifically, collagen fibers). Cells and fibers "push and pull" on one another while the heart beats: this is called mechanical coupling. Because hypertension alters the composition of the tissue -- cells become bigger and fibers grow in number -- it is intuitive to think that it will also have an impact on how cells and fibers interact. The goal of this project is to use advanced modeling and computations and careful experiments to understand how hypertension affects the mechanical coupling and how this change in coupling contributes to cardiac dysfunction. This study will have impact in the fields of regenerative medicine and tissue engineering, specifically in the case of new emerging heart failure treatments. Finally, this project will also serve as a platform to launch an innovative outreach program ("I heart Biomechanics") to educate and enhance public awareness of biomechanics research.
In this project, it is hypothesized that the mechanical coupling between cells and collagen fiber network not only changes during pathological remodeling in the heart of hypertensive rats, but also is one of the significant forces driving remodeling. The overarching goal of this project is to elucidate how mechanical coupling between cells and extracellular matrix (1) drives microstructural changes in healthy and diseased hearts, (2) affects mechanical properties of the left ventricle at various stages of the remodeling, and (3) contributes to the pathological changes of the heart tissue. The approach consists of new constitutive formulations, finite element modeling, and experiments on intact tissues as well as tissues with isolated components under both active and passive conditions. In the process, a methodology will also be developed to quantify and incorporate the collagen-cells mechanical coupling into a new microstructural model for ventricular mechanics.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
