Bunch et al. describe a new assay to rapidly evaluate binding of cMyBP-C to F-actin (with or without tropomyosin) in solution. Changes in labeled actin fluorescence lifetime due to cMyBP-C phosphorylation and/or HCM mutations were consistent with measurements obtained using cosedimentation assays.

In this study, Kawai et al. address the role of inorganic phosphate in muscle cross-bridge kinetics using a subcellular structure called myofibrils. They demonstrate that phosphate binding is a key determinant of oscillatory work and suggest that it may also compete with ATP for binding to the myosin head.

Giles et al. show that the phosphorylation status of cardiac myosin-binding protein-C (cMyBP-C) modulates Ca2+ activation–dependent unloaded shortening velocity of skinned myocardium. The results suggest that cMyBP-C phosphorylation regulates cooperative binding of myosin to actin, and thus the activation state of the thin filament.

Sanchez et al. target the Ca2+-sensitive dye CGaMP6f to the triad region of the sarcomere by using the T306 domain of triadin. Their approach reveals synchronous Ca2+ release across individual triads and will facilitate the study of ryanodine receptor channel function.

van der Horst et al. show that dynein, a microtubule motor protein, carries the voltage-gated potassium channel Kv7.4 away from the cell membrane in vascular smooth muscle cells, thereby reducing its functional impact. These data have implications for our understanding of arterial contractility.

Using super-resolution fluorescence microscopy and in silico simulations, Rahmanseresht et al. demonstrate that the N terminus of myosin-binding protein C (MyBP-C) tends to bind to actin filaments in both active and relaxed muscle. Binding to the myosin head also appears possible but only when the myosin head is near the actin filament.

Our multiscale modeling approach incorporates the spatial and chemomechanical properties of sarcomeres for simulation of the mechanical performance of striated muscle. In this study, we demonstrate the ability to simulate the twitch tension and kinetics of cardiac muscle, and this requires inclusion of muscle elasticity and thick-filament regulation. The model provides precise simulations of twitch contractions in rat cardiac muscle, and the parameters used can accurately predict the Ca2+ sensitivity of force in an intact muscle.