“Mend a Broken Heart: Bioengineering the electrical, the Ca2+ signaling, and the mechanical systems.”
Three dynamic systems – the electrical system, the Ca2+ signaling system, and the mechanical system – control the rhythm and the strength of heart beats. In the classic paradigm, the electrical excitation controls the Ca2+ signaling which, in turn, controls the muscle contraction. Most previous work focused on each dynamic system in isolation. However, recent advancements reveal that defects in the Ca2+ signaling system and the contractile system can feedback to cause electric arrhythmias. Such feedback mechanisms underlie many heart diseases including hypertension-induced heart failure, hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM). We have developed innovative techniques and new methods to investigate the cellular and molecular mechanisms that control these systems’ function in health and diseases. In particular, I will present our newly developed ‘Cell-in-Gel’ system that allows embedding single cells in a 3-D elastic matrix. When the live muscle cell contract in-gel, the elastic gel matrix deforms and imposes longitudinal tension, transverse compression, and surface traction on the cell. We found that when myocytes contract under mechanical stress, the Ca2+ transient was increased to enhance contraction during systole, but can also cause arrhythmogenic Ca2+ activities during diastole. Currently we are using these new techniques to investigate the mechano-chemo-transduction mechanisms and to fingerprint drug effects for developing new anti-arrhythmic drugs.
Because the electrical system, the Ca2+ signaling system, and the mechanical system are ubiquitous and control the function of many biological cells, the methods we develop are of general use for interrogating these systems in various cells types.
When: Thursday, October 31, 2013 4:10 PM
Where: 1005 GBSF