The overall goal of this CAREER project is to establish a novel parallel computational framework of multiscale geometric modeling and mesh generation that can be applied to cardiac biomechanics applications. This capability will enable accurate, stable, efficient simulations of many biological processes such as calcium (Ca2+) mediated signaling, excitation-contraction coupling and energy metabolism in cardiac muscle cells, and lead to great advances in cardiac biomechanics. In cardiac muscle cells, Ca2+ is best known for its role in contraction activation. Alterations in Ca2+ distributions are now recognized to be the primary mechanisms of cardiac dysfunction in a diverse range of common pathologies including cardiac arrhythmias and hypertrophy. To predict and analyze how Ca2+ dynamics and cardiac excitation-contraction coupling are regulated, modeling of realistic geometries of large, complicated t-tubule network and associated protein complexes is needed. However, previous studies have been limited to simplified geometries. In this project, the PI focuses on 1) multiscale geometric modeling for protein complexes starting from atomic resolution data in the Protein Data Bank; 2) parallel mesh generation with topology ambiguity resolved and curvature-driven quality improvement; and 3) model validation in adaptive finite element analysis of Ca2+ signaling in ventricular myocytes with complicated realistic geometry. To handle such large, complicated systems, multicore parallel meshing toolkits will be developed and encapsulated with the simulation software.
The proposed research will attain the highest degree of accuracy, efficiency and robustness in model development and simulation. It will significantly advance predictive capability in cardiac applications, and the understanding of anatomical and physiological properties at molecular and cellular scales. This parallel computational infrastructure can also be used for other complicated systems, providing engineers and scientists with novel technologies to construct accurate computer models. Furthermore, this interdisciplinary project will integrate research and education via novel educational tool and curriculum development as well as outreach activities. Students will interact with collaborative institutions to gain firsthand experience of real issues. Women, minority groups and high school students will be included in the proposed research and education activities through CMU's K-12 Programs. Education activities will be assessed in conjunction with CMU's Eberly Center for Teaching Excellence.
