myosin interaction
Recently Published Documents

AbstractIn this work we provide a novel energy-consistent formulation for the classical 1D formulation of blood flow in an arterial segment. The resulting reformulation is shown to be suitable for the coupling with a lumped (0D) model of the heart that incorporates a reduced formulation of the actin-myosin interaction. The coupling being consistent with energy balances, we provide a complete heart-circulation model compatible with thermodynamics hence stable numerically and informative physiologically. These latter two properties are verified by numerical experiments.

AbstractA coupled electromechanical model to describe the transduction process of cellular electrical activity into mechanical deformation has been presented. The model consolidates a biophysical smooth muscle cell model, a biophysical actin-myosin interaction model, a sliding filament model and a viscoelastic constitutive model to construct an active finite viscoelastic model. The key input to this model is an electrical pulse which then estimates the resulting stress and deformation in the cell. The proposed model was used to recreate experimental observations performed on canine and porcine gastric tissue strips. In all cases, the simulation results were well matched with the experimental data (R2> 0.9).

Muscular contraction is a fundamental phenomenon in all animals; without it life as we know it would be impossible. The basic mechanism in muscle, including heart muscle, involves the interaction of the protein filaments myosin and actin. Motility in all cells is also partly based on similar interactions of actin filaments with non-muscle myosins. Early studies of muscle contraction have informed later studies of these cellular actin-myosin systems. In muscles, projections on the myosin filaments, the so-called myosin heads or cross-bridges, interact with the nearby actin filaments and, in a mechanism powered by ATP-hydrolysis, they move the actin filaments past them in a kind of cyclic rowing action to produce the macroscopic muscular movements of which we are all aware. In this special issue the papers and reviews address different aspects of the actin-myosin interaction in muscle as studied by a plethora of complementary techniques. The present overview provides a brief and elementary introduction to muscle structure and function and the techniques used to study it. It goes on to give more detailed descriptions of what is known about muscle components and the cross-bridge cycle using structural biology techniques, particularly protein crystallography, electron microscopy and X-ray diffraction. It then has a quick look at muscle mechanics and it summarises what can be learnt about how muscle works based on the other studies covered in the different papers in the special issue. A picture emerges of the main molecular steps involved in the force-producing process; steps that are also likely to be seen in non-muscle myosin interactions with cellular actin filaments. Finally, the remarkable advances made in studying the effects of mutations in the contractile assembly in causing specific muscle diseases, particularly those in heart muscle, are outlined and discussed.

Inotropes historically all increased intra-cellular calcium levels and they commonly caused intracellular Ca2+ overload and triggered malignant arrhythmias. The myosin activators, such as Omecamtiv Mecarbil (OM), increase myosin activity and function, and modify acto-myosin interaction through calcium-independent mechanisms. OM is a selective cardiac myosin activator that binds specifically the catalytic domain of cardiac myosin without any significant effect over other types of non-cardiac myosin. It increases the speed of ATP hydrolysis and, therefore, accelerates the transition rate to a strongly bound force-producing state, increases the number of myosin heads that interact with actin filaments and increases the proportion of time they are in a force producing state. OM decreases the inefficient use of non-contractile energy. OM has been studied in 4 phase II clinical trials with more than 1,300 patients with heart failure. The GALACTIC-HF trial is a nearly 8,000 patient HFrEF mortality/morbidity trial which started recruiting in January 2017 and should be completed soon.