2015 New Initiative Grant
Andrea J. Liu, Ph.D. (PI) Hepburn Professor of Physics, University of Pennsylvania
Benjamin L. Prosser (co-PI) Assistant Professor of Physiology, University of Pennsylvania
Dennis E. Discher (co-PI) Robert D. Bent Professor of Chemical and Biomolecular Engineering, University of Pennsylvania
Mechanical signaling in early hearts: Theory & Experiment
Abstract
In the beating heart, cells called cardiomyocytes contract in a coordinated fashion to generate a contractile wavefront that propagates from through the heart with each beat to pump blood. This wavefront has been understood for decades as an electrical reaction-diffusion nonlinear phenomenon: once the voltage across the cell membrane crosses threshold for an action potential, ions enter the cell, ultimately leading to cell contraction and ion flux to push the voltage across threshold in the next cell. Thus, the heart has been regarded as an electrically-excitable system: the contractile wavefront propagates at constant velocity without decaying because it is amplified as it goes. However, we recently discovered that the speed of the contractile wavefront depends strongly on the stiffness of heart tissue in the developing chicken embryo. We have hypothesized that contraction of a cardiomyocyte induces strain in neighboring cells, ultimately causing them to contract in response. The embryonic heart could thus be called a "mechanically-excitable" system, in which stress diffuses, and a sufficiently high local mechanical stress triggers generation of additional stress. The primary aim of this proposal is to test this hypothesis in the embryonic chicken heart and to elucidate the role of mechanical excitability in the adult heart. If verified, these ideas could transform the way we think about how this first organ in the embryo– the heart–develops and functions.