Herzog, WalterLeonard, Timothy R.Joumaa, VenusDuVall, Michael M.Panchangam, Appaji2018-10-092018-10-092012-01Herzog, W., Leonard, T., Joumaa, V., DuVall, M., & Panchangam, A. (2012). The three filament model of skeletal muscle stability and force production. MCB Molecular and Cellular Biomechanics, 9(3), 175-191.1556-5300http://hdl.handle.net/1880/108815Ever since the 1950s, muscle force regulation has been associated with the cross-bridge interactions between the two contractile filaments, actin and myosin. This gave rise to what is referred to as the "two-filament sarcomere model". This model does not predict eccentric muscle contractions well, produces instability of myosin alignment and force production on the descending limb of the force-length relationship, and cannot account for the vastly decreased ATP requirements of actively stretched muscles. Over the past decade, we and others, identified that a third myofilament, titin, plays an important role in stabilizing the sarcomere and the myosin filament. Here, we demonstrate additionally how titin is an active participant in muscle force regulation by changing its stiffness in an activation/force dependent manner and by binding to actin, thereby adjusting its free spring length. Therefore, we propose that skeletal muscle force regulation is based on a three filament model that includes titin, rather than a two filament model consisting only of actin and myosin filaments consisting only of actin and myosin filamentsenUnless 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.https://creativecommons.org/licenses/by/4.0muscletitincross bridgejournal article10.11575/PRISM/33155