Cellular Biophysics

Michael D Stern, MD, Chief

The Cellular Biophysics Section continues a 30-year program of studying the mechanisms by which calcium acts as a signaling molecule within individual heart muscle cells, to trigger the contraction of the muscle and regulate the membrane ion currents that synchronize the beating of the whole heart. We use a combination of experimental measurements employing fluorescent probes in single cells, together with extensive mathematical modeling of the underlying molecular physics, utilizing NIH supercomputing resources. In recent years we have concentrated on the process of calcium-induced calcium release, in which small calcium signals trigger larger ones, resulting in propagated wavelets of calcium that play a crucial role in generating both the normal heart rhythm and life-threatening arrhythmias.

A spinoff from our modeling work is a separate project studying the in-silico evolution of populations of virtual organisms. This work aims to find abstract, underlying regularities in the working of Darwinian natural selection, which may apply also to cultural evolution. We also repurposed our computational method to study the dynamics of the recent COVID epidemic.

Portfolio/Research Areas

• Cardiac excitation contraction coupling
• Calcium sparks and CICR by ryanodine receptors
• Simulation of calcium dynamics in pacemaker cells
• Mechanism of the "calcium clock" underlying the normal heart rate
• Intra-cellular dynamics in human heart cells, using numerical and statistical.
• Simulation of "artificial life" virtual organisms
• Theoretical studies of evolutionary mechanisms underlying human behavior
   

Findings and Publications

1. Maltsev VA, Stern MD. The paradigm shift: Heartbeat initiation without "the pacemaker cell". Front Physiol. 2022 Dec 9;13:1090162. doi: 10.3389/fphys.2022.1090162. · PMID: 36569749 PMCID: PMC9780451
    
2. Maltsev AV, Stern MD, Lakatta EG, Maltsev VA. Functional Heterogeneity of Cell Populations Increases Robustness of Pacemaker Function in a Numerical Model of the Sinoatrial Node Tissue. Front Physiol. 2022 Apr 27;13:845634. doi: 10.3389/fphys.2022.845634 · PMID: 35574456 · PMCID: PMC9091312
    
3. Anna V. Maltsev, Michael D. Stern, Victor A. Maltsev. Disorder in Ca2+ Release Unit Locations Confers Robustness but Cuts Flexibility of Heart Pacemaking. Journal of General Physiology 2022: Sep 5;154(9):e202113061. Doi: 10.1085/jgp.202113061