Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.
G, A., M, D., W, M., B, S., N, P., M, S., J, Y., J, Z., R, C., & R, K. (2026). Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.. eLife. https://doi.org/10.7554/eLife.107730
G A, M D, W M, B S, N P, M S, et al. Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.. eLife. 2026; doi: 10.7554/eLife.107730
G A, M D, W M, et al. Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.[J]. eLife. 2026. DOI: 10.7554/eLife.107730.
@article{g2026,
author = {Arecchi G and Dente M and Ma W and Scellini B and Piroddi N and Scardigli M and Yu J and Zhao J and Cicchi R and Kinegawa R},
title = {Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.},
journal = {eLife},
year = {2026},
doi = {10.7554/eLife.107730},
note = {PMID: 42606952},
}
TY - JOUR AU - Arecchi G AU - Dente M AU - Ma W AU - Scellini B AU - Piroddi N AU - Scardigli M AU - Yu J AU - Zhao J AU - Cicchi R AU - Kinegawa R TI - Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy. T2 - eLife PY - 2026 DO - 10.7554/eLife.107730 AN - PMID:42606952 ER -
This study explores the use of polarized second-harmonic generation (pSHG) to investigate myosin conformation in the relaxed state, differentiating between the actin-available, disordered (ON) state and the energy-conserving, ordered (OFF) state. By shifting the ON/OFF equilibrium using both physical and chemical manipulations, we demonstrate the sensitivity of pSHG in quantifying the ON/OFF ratio in skeletal and cardiac tissues. Comparisons with X-ray diffraction measurements further validate our findings. Applying this approach to a sarcomeric mutation associated with hypertrophic cardiomyopathy, we show that R403Q/MYH7-mutated minipig ventricle tissue exhibits a higher ON fraction compared to controls. This difference is abolished under high concentrations of a myosin activator (2-deoxyATP) and an inhibitor (Mavacamten), indicating structural similarity between R403Q and controls in these two states. ATPase assays reveal increased resting ATPase activity in R403Q samples, which persists even in the presence of 2-deoxyATP, suggesting that the elevated energy consumption in the R403Q mutation is driven by both a population shift toward the ON state and enhanced myosin ATPase activity per motor head.