Research Focus

Contraction-relaxation function and mechanochemical coupling of myofibrils

Function of Contraction/Relaxation and Mechanical-Chemical Coupling of Myofibrils

The primary function of cardiomyocytes (CMs), to generate force and shorten in length, occurs when the subcellular myofibrils contract due to multiple interactions between ATPase-driven myosin motors and actin filaments. Myofibrils consist of many sarcomeres arranged in series, which directly control the contraction-relaxation events of cardiac muscle cells during cyclic variations in intracellular Ca²⁺ concentration. Therefore, isolated myofibrils serve as a contractile model used to understand processe involving sarcomeric proteins that determine the contractile function of cardiac muscle cells in the absence of Ca²⁺ handling systems and upstream signals.

Myofibrils can be studied using fast kinetic, micromechanical, and chemical techniques because they are thin and are in rapid diffusion equilibrium with their environment. We have established a micromechanical setup that uses an nNewton-sensitive force sensor. This setup allows for rapid switching of the solutions to which the myofibrils are exposed, and the force-kinetic parameters of myofibrillar activation and relaxation at various Ca²⁺ concentrations can be analyzed with high temporal resolution. Various established biochemical methods can determine the steady-state or transient ATPase activity of the sarcomeric myosin motor using mechanically unloaded, native myofibrils.These studies can enable a correlation between biochemical events and mechanical events during the cross-bridge cycle based on the isoform composition of sarcomeric proteins.

Subcellular myofibrils can be isolated from human (e.g., biopsies), human-derived, and non-human cardiac and skeletal muscle cells (e.g., mouse, rat, rabbit, zebrafish, and hESC/hiPSC-CMs).

For more information, please visit the Iorga Research Group’s website.