Abstract: Sarcomeric missense mutations affect striated muscle contractility and can lead to various types of inherited cardiac diseases such as, hypertrophic and dilated cardiomyopathies. The majority of these mutations have found to be distributed on residues located at the interfaces of many proteins of the sarcomere that regulates cardiac contraction. These mutations and post-translational modifications influence not only contraction dynamics, but affect myofilament calcium sensitivity and alter cooperative interactions between the sarcomere regulatory proteins. Although, several Monte Carlo type myofilament models attempt to investigate and/or to predict the functional effects of point mutations on sarcomere contractility, the exact molecular-to-filament mechanism by which these alterations provide the trigger for disease progression and remodeling is still remaining poorly understood. In this talk, I will present a novel molecular-to-filament multiscale myofilament model that can describe the activation process of the thin filament during sarcomere contraction. The model is based on the Brownian flashing ratchet theory for the molecular scale and is using Langevin dynamics stochastic principle for the filament scale. This model is then integrated into a finite element model for the electro-mechanical coupling of tissue and organ scales in order to predict the phenotype remodeling of cardiac function during arrhythmia and heart failure.

Bio: Yasser Aboelkassem is currently an assistant research scientist in the Department of Bioengineering at UC San Diego. He obtained his bachelor’s degree in aeronautics from Cairo University and his master’s degree in mathematics and doctorate in mechanics from Virginia Tech. Aboelkassem was a postdoctoral associate in the Department of Biomedical Engineering and Medicine at Johns Hopkins University, and prior to that he was a postdoctoral fellow in the Department of Biomedical Engineering and School of Medicine at Yale University. He recently obtained his mini-MBA degree from Rady School of Management at UC San Diego. Aboelkassem’s research focuses on multiscale modeling of cardiac mechanics and fluid transport in the human cardiovascular system. He uses computational and experimental tools to investigate the relationships between the cellular and extracellular structure of cardiac muscle as well as the hemodynamics, electrical, and mechanical function of the whole heart during cardiac diseases.