11:15-12:15 Decoding the Mysteries of Protein Mechanostability
Rafael Bernardi
Auburn University
The behavior of proteins under mechanical stress coordinates a myriad of biological processes, ranging from pathogen adhesion to cell motility. Despite its pivotal role, a comprehensive understanding of protein mechanostability has long remained elusive. In this talk, I will introduce a new approach that combines Molecular Dynamics Simulations, Network Analysis, Artificial Intelligence, and Onsager’s Reciprocal Relations to dissect this complex landscape. Our interdisciplinary methodology has been applied across various biological systems, including bacterial adhesion mechanisms, SARS-CoV-2 spike proteins, and cellulosomes. Using case studies such as the virulence of methicillin-resistant Staphylococcus aureus (MRSA) and the mechanics of SARS-CoV-2, I will illustrate how our network-based analysis provides unparalleled insights into protein behavior under stress. This approach not only serves as a potent tool for studying macromolecular complexes but also lays the groundwork for innovative therapeutic solutions. Join me to explore this exciting frontier where physics, biology, chemistry, and computational science converge to unlock new avenues for understanding and manipulating the biological world.
Cardiac conduction is the process by which electrical excitation spreads through the heart, triggering individual myocytes to contract in synchrony. Defects in conduction disrupt synchronous activation and are associated with life-threatening arrhythmias in many pathologies. For over a century, cardiac conduction has been viewed as occurring solely through the direct flow of ionic current from cell to cell via gap junctions. However, this view was challenged as early as 1960 based on studies in avian hearts, where conduction occurs in the near total absence of gap junctions. Since then, a growing body of phenomena that cannot be well explained by electrotonic coupling alone have led some to hypothesize a role for ephaptic coupling in cardiac conduction. This non-canonical mechanism, which is known to occur in other tissues such as the brain and the retina, envisions cells communicating via electrochemical transients within restricted nanodomains at cell-cell contacts. In recent years, we and others have used experimental and modeling approaches to provide strong evidence supporting a role for ephaptic coupling in the heart and identified ion channel-rich nanodomains within intercalated discs (cell-cell contact sites) as candidates for the cardiac ephapse. In addition to expanding our theoretical understanding of cardiac conduction and explaining seemingly paradoxical experimental and clinical findings, this work has yielded important insights into the mechanisms of cardiac arrhythmia and enabled us to develop novel antiarrhythmic therapies.
Last update: 9/13/2023, Ralf Bundschuh