The contributions of filaments and cross-bridges to sarcomere compliance in skeletal muscle

Elisabetta Brunello, Marco Caremani, Luca Melli, Marco Linari, Manuel Fernandez-Martinez, Theyencheri Narayanan, Malcolm Irving, Gabriella Piazzesi, Vincenzo Lombardi*, Massimo Reconditi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Force generation in the muscle sarcomere is driven by the head domain of the myosin molecule extending from the thick filament to form cross-bridges with the actin-containing thin filament. Following attachment, a structural working stroke in the head pulls the thin filament towards the centre of the sarcomere, producing, under unloaded conditions, a filament sliding of ~11 nm. The mechanism of force generation by the myosin head depends on the relationship between cross-bridge force and movement, which is determined by compliances of the cross-bridge (Ccb) and filaments. By measuring the force dependence of the spacing of the high-order myosin- and actin-based X-ray reflections from sartorius muscles of Rana esculenta we find a combined filament compliance (Cf) of 13.1 ± 1.2 nm MPa-1, close to recent estimates from single fibre mechanics (12.8 ± 0.5 nm MPa-1). Ccb calculated using these estimates is 0.37 ± 0.12 nm pN-1, a value fully accounted for by the compliance of the myosin head domain, 0.38 ± 0.06 nm pN-1, obtained from the intensity changes of the 14.5 nm myosin-based X-ray reflection in response to 3 kHz oscillations imposed on single muscle fibres in rigor. Thus, a significant contribution to Ccb from the myosin tail that joins the head to the thick filament is excluded. The low Ccb value indicates that the myosin head generates isometric force by a small sub-step of the 11 nm stroke that drives filament sliding at low load. The implications of these results for the mechanism of force generation by myosins have general relevance for cardiac and non-muscle myosins as well as for skeletal muscle.

Original languageEnglish
Pages (from-to)3881-3899
Number of pages19
JournalThe Journal of physiology
Volume592
Issue number17
DOIs
Publication statusPublished - 1 Sept 2014

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