Stanford Medicine

Mechanotransduction

Cellular Mechanics

Our laboratory is interested in understanding the fundamental mechanisms responsible for heart failure and arrhythmia. The precise derangements that account for these processes at the cellular level are incompletely understood. In particular, the mechanisms by which the cardiac molecular motors malfunction have not yet been well described. Along with our collaborator, Dr James Spudich we are working to understand how cardiac contractility becomes altered in disease, and how that alteration feeds back on the disease process. We have been working to measure single cell force production in heart failure cells and are combining this with measurements of excitation-contraction coupling. We are particularly interested in hypertrophic and dilated cardiomyopathy and we have recently taken advantage of the ability to derive inducible pluripotent stem cells from patients through our collaboration with Dr. Joseph Wu. These model cell systems provide an exciting new avenue through which to approach translational myocardial biology.

Cell Mechanics

Cardiac function through stretch. Upper left panel shows a picture of a single adult cardiomyocyte before (top) and after (bottom) stretch with carbon microfibers. This stretch done sequentially while pacing the cell allows singel cell force measurements to be made by carbon fiber bending. In the right upper panel, using this approach, the single cell frank-starling effect is seen. When force measurements from these carbon microfibers are put together with evoked calcium transient measurements, the calcium force frequency relationship can be investigated as shown in the bottom left panel. In the lower right panel, stretch-induced fibrillation of the muscle fiber is shown at induction and then recovery using a combination of rapid pacing and re-stretch.