Issues

Dvornikov et al. test a new high-throughput fluorescence lifetime-based assay using a human cardiac troponin C probe in cardiac myofibrils. The assay sensitivity and precision allow for the detection of key structural changes in cTnC that reports changes in thick and filament proteins in health and disease, which promises to have utility in screening therapeutic compounds that target these proteins.

The activation status of thin filaments determines cooperativity between neighboring myosin heads in muscle.

Isometric force–pCa relationships were measured in human myocardial strips at 37°C. Ca²⁺ sensitivity increased with sarcomere length in samples from donors and patients with ischemic heart failure. Ca²⁺ sensitivity did not change with length in samples from patients with non-ischemic heart failure.

Ananchenko and Musgaard use multiscale MD simulations to predict an outer leaflet PUFA-binding region on the ASIC protein transmembrane domain, building on existing functional data, and further supporting direct interactions of PUFAs with ASICs.

Cryo-EM was used to elucidate high-resolution structures of actin-tropomyosin filaments decorated with human cardiac myosin in the rigor and ADP-bound states. Differences in the myosin lever arm orientation correlate with the overall actomyosin-linked force-sensitivity.

ROS-dependent dissociation of FKBP12.6 mediates pulmonary artery vasoconstriction and pulmonary hypertension.

This Viewpoint uncovers the phylogenetic, structural, and functional diversity of membrane mechanosensors, recent successes, and the on-going challenges for studying them in reconstituted systems and intact cells, tissues, plants, and animals.