Open Access

REVIEW

The Three Filament Model of Skeletal Muscle Stability and Force Production

Walter Herzog^∗, Tim Leonard^†, Venus Joumaa^‡, Michael DuVall^§, Appaji Panchangam^¶

∗ University of Calgary, 2500 University Drive NW, KNB 402, Calgary, AB T2N 1N4, walter@kin.ucalgary.ca
† University of Calgary, 2500 University Drive NW, KNB 401, Calgary, AB T2N 1N4, leonard@kin.ucalgary.ca
‡ Lebanese International University, Schools of Engineering and Arts and Sciences, Bekaa, Lebanon
§ University of Calgary, 2500 University Drive NW, KNB 404, Calgary, AB T2N 1N4.
¶ University of Calgary, 2500 University Drive NW, KNB 404, Calgary, AB T2N 1N4.

Molecular & Cellular Biomechanics 2012, 9(3), 175-192. https://doi.org/10.3970/mcb.2012.009.175

Abstract

Ever 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.

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