Herzog, WalterSchappacher-Tilp, Gudrun2023-06-232023-06-232023-06Herzog, W., & Gudrun Schappacher-Tilp, G. (2023, June). Molecular Mechanisms of Muscle Contraction: A Historical Perspective. Journal of Biomechancis, 155(2023), 111659. https://doi.org/10.1016/j.jbiomech.2023.1116590021-9290https://hdl.handle.net/1880/116657Studies of muscle structure and function can be traced to at least 2,000 years ago. However, the modern era of muscle contraction mechanisms started in the 1950s with the classic works by AF Huxley and HE Huxley, both born in the United Kingdom, but not related and working independently. HE Huxley was the first to suggest that muscle contraction occurred through the sliding of two sets of filamentous structures (actin or thin filaments and myosin or thick filaments). AF Huxley then developed a biologically inspired mathematical model suggesting a possible molecular mechanism of how this sliding of actin and myosin might take place. This model then evolved from a two-state to a multi-state model of myosin-actin interactions, and from one that suggested a linear motor causing the sliding to a rotating motor. This model, the cross-bridge model of muscle contraction, is still widely used in biomechanics, and even the more sophisticated cross-bridge models of today still contain many of the features originally proposed by AF Huxley. In 2002, we discovered a hitherto unknown property of muscle contraction that suggested the involvement of passive structures in active force production, the so-called passive force enhancement. It was quickly revealed that this passive force enhancement was caused by the filamentous protein titin, and the three-filament (actin, myosin, and titin) sarcomere model of muscle contraction evolved. There are many suggestions of how these three proteins interact to cause contraction and produce active force, and one such suggestion is described here, but the molecular details of this proposed mechanism still need careful evaluation.enUnless otherwise indicated, this material is protected by copyright and has been made available with authorization from the copyright owner. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Skeletal muscletitinactinmyosinresidual force enhancementpassive force enhancementresidual 7 force depressiontheories of contractionmathematical models of contractionArticlehttps://doi.org/10.1016/j.jbiomech.2023.111659