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Cellular Biophysics

Michael D Stern, MD, Chief

The Cellular Biophysics Section continues a 30 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 using 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 arhythmias.

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.

List of 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
  • Simulation of "artificial life" virtual organisms
  • Theoretical studies of evolutionary mechanisms underlying human behavior

Findings and Publications

Stern MD, Maltseva LA, Juhaszova M, Sollott SJ, Lakatta EG, Maltsev VA. Hierarchical clustering of ryanodine receptors enables emergence of a calcium clock in sinoatrial node cells.  J Gen Physiol. 2014 May;143(5):577-604. doi: 10.1085/jgp.201311123.

Maltsev, V. A., Yaniv, Y., Maltsev, A. V., Stern, M. D., & Lakatta, E. G. (2014). Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell. Journal of Pharmacological Sciences, 125(1), 6–38.

Stern, M. D., Ríos, E., & Maltsev, V. A. (2013). Life and death of a cardiac calcium spark. The Journal of General Physiology, 142(3), 257–274. http://doi.org/10.1085/jgp.201311034

Maltsev, A. V., Maltsev, V. A., Mikheev, M., Maltseva, L. A., Sirenko, S. G., Lakatta, E. G., & Stern, M. D. (2011). Synchronization of Stochastic Ca2+Release Units Creates a Rhythmic Ca2+ Clock in Cardiac Pacemaker Cells. Biophysical Journal, 100(2), 271–283. http://doi.org/10.1016/j.bpj.2010.11.081

Stern, M. D. (2010). Patrimony and the Evolution of Risk-Taking. PLoS ONE, 5(7), e11656. http://doi.org/10.1371/journal.pone.0011656

Josephson, I. R., Guia, A., Lakatta, E. G., Lederer, W. J., & Stern, M. D. (2010). Ca2+-dependent components of inactivation of unitary cardiac L-type Ca2+channels. The Journal of Physiology, 588(Pt 1), 213–223. http://doi.org/10.1113/jphysiol.2009.178343

Stern, M. D. (1999). Emergence of homeostasis and “noise imprinting” in an evolution model. Proceedings of the National Academy of Sciences of the United States of America, 96(19), 10746–10751.

Stern, M. D., Song, L.-S., Cheng, H., Sham, J. S. K., Yang, H. T., Boheler, K. R., & Ríos, E. (1999). Local Control Models of Cardiac Excitation–Contraction Coupling  : A Possible Role for Allosteric Interactions between Ryanodine Receptors. The Journal of General Physiology, 113(3), 469–489.

Cheng, H., Song, L. S., Shirokova, N., González, A., Lakatta, E. G., Ríos, E., & Stern, M. D. (1999). Amplitude distribution of calcium sparks in confocal images: theory and studies with an automatic detection method. Biophysical Journal, 76(2), 606–617.

Stern, M. D., Pizarro, G., & Ríos, E. (1997). Local Control Model of Excitation–Contraction Coupling in Skeletal Muscle. The Journal of General Physiology, 110(4), 415–440.

Stern, M.D., (1993). Two-fiber laser Doppler velocimetry in blood: Monte Carlo simulation in three dimensions. Appl Opt. 1993 Feb 1;32(4):468-76. doi: 10.1364/AO.32.000468.

Stern, M. D. (1992). Theory of excitation-contraction coupling in cardiac muscle. Biophysical Journal, 63(2), 497–517.