Ising models of cooperativity in muscle contraction
Year: 2026
Authors: Saadat E., Caruel M., Gherardini S., Morotti I., Marcello M., Caremani M., Linari M., Latella I., Ruffo S.
Autors Affiliation: SISSA, Via Bonomea 265, I-34136 Trieste, Italy; Univ Paris Est Creteil, Univ Gustave Eiffel, CNRS, UMR 8208,MSME, F-94010 Creteil, France; Consiglio Nazl Ric CNR INO, Ist Nazl Ottica, Largo Enrico Fermi 6, I-50125 Florence, Italy; Univ Florence, Dept Biol, I-50019 Sesto Fiorentino, Italy; Univ Florence, PhysioLab, I-50019 Sesto Fiorentino, Italy; Univ Barcelona, Dept Fis Mat Condensada, Marti & Franques 1, Barcelona 08028, Spain; Univ Barcelona IN2UB, Inst Nanociencia & Nanotecnol, Diagonal 645, Barcelona 08028, Spain; CNR, Ist Sistemi Complessi, Via Madonna Piano 10, I-50019 Sesto Fiorentino, Italy; INFN, Sez Firenze, Florence, Italy.
Abstract: Regulation of contraction in striated muscle is controlled by a dual mechanism involving both thin filaments containing actin and thick filaments containing myosin. The thin filament is activated by calcium ions binding to troponin, leading to tropomyosin azimuthal displacement, which allows the activation of a regulatory unit (composed of one troponin, one tropomyosin, and seven actin monomers) that exposes the actin sites for interaction with the myosin motors. Motor attachment to actin contributes to spreading activation within and beyond a regulatory unit along the thin filament through a cooperative mechanism. We introduce a one-dimensional Ising model to elucidate the mechanism of cooperativity in thin filament activation in relation to the force generated by the attached myosin motor. The model characterizes thin filament activation and cooperativity using only two parameters: one related to calcium concentration and the other to the force exerted by the attached myosin motor, which is modulated by temperature. At any force, the model is able to determine the extent of actin-myosin interactions on a correlation length ranging from two to seven actin monomers, in addition to the seven actin monomers of the regulatory unit. Our theoretical predictions are successfully tested on experimental data, and our tests also include the condition of hindered filament activation by the use of the specific drug omecamtiv mecarbil (OM). According to our model, the effect of OM results in an anticooperativity mechanism accounting for the experimental data.
Journal/Review: PHYSICAL REVIEW E
Volume: 113 (4) Pages from: 44408-1 to: 44408-10
More Information: We thank Vincenzo Lombardi and Massimo Reconditi for continuous discussion and critical reading of the manuscript. I.L. acknowledges financial support from the Spanish Government through Grants No. PID2021-126570NB-I00 and No. PID2024-156516NB-I00 financed by MICIU/AEI/10.13039/501100011033 and FEDER/UE. S.G., S.R., and M.L. acknowledge financial support from the European Union-NextGeneration EU within PRIN 2022, PNRR, Project No. P2022XPT32 Regulation of striated muscle: a research bridging single molecule to organ (ResTriMus) (CUP B53D23033290001).KeyWords: Skeletal-muscle; Myosin Filament; Unified Theory; Activation; Force; Heart; Binding; Fibers; ActinDOI: 10.1103/hpqb-dc8h
