Preprint Article Version 1 This version is not peer-reviewed

Myosin Cross-bridge Behaviour in Contracting Muscle – The T1 Curve of Huxley & Simmons (1971) Revisited

Version 1 : Received: 12 March 2019 / Approved: 14 March 2019 / Online: 14 March 2019 (07:01:45 CET)

How to cite: Knupp, C.; Squire, J.M. Myosin Cross-bridge Behaviour in Contracting Muscle – The T1 Curve of Huxley & Simmons (1971) Revisited. Preprints 2019, 2019030147 (doi: 10.20944/preprints201903.0147.v1). Knupp, C.; Squire, J.M. Myosin Cross-bridge Behaviour in Contracting Muscle – The T1 Curve of Huxley & Simmons (1971) Revisited. Preprints 2019, 2019030147 (doi: 10.20944/preprints201903.0147.v1).

Abstract

The stiffness of the myosin cross-bridges is a key factor in analysing possible scenarios to explain myosin head changes during force generation in active muscles.  The seminal study of Huxley and Simmons (1971: Nature 233: 533) suggested that most of the observed half-sarcomere instantaneous compliance (=1/stiffness) resides in the myosin heads.    They showed with a so-called T1 plot that, after a very fast release, the half-sarcomere tension reduced to zero after a step size of about 60Å (later with improved experiments reduced to 40Å).   However, later X-ray diffraction studies showed that myosin and actin filaments themselves stretch slightly under tension, which means that most (at least two-thirds) of the half sarcomere compliance comes from the filaments and not from cross-bridges.    Here we have used a different approach, namely to model the compliances in a virtual half sarcomere structure in silico.   We confirm that the T1 curve comes almost entirely from length changes in the myosin and actin filaments, because the calculated cross-bridge stiffness (probably greater than 0.4 pN/Å) is higher than previous studies have suggested.    In the light of this, we present a plausible modified scenario to describe aspects of the myosin cross-bridge cycle in active muscle.   In particular, we suggest that, apart from the filament compliances, most of the cross-bridge contribution to the instantaneous T1 response comes from weakly-bound myosin heads, not myosin heads in strongly attached states.   The strongly attached heads would still contribute to the T1 curve, but only in a very minor way, with a stiffness that we postulate could be around 0.1 pN/Å, a value which would generate a working stroke close to 100 Å from the hydrolysis of one ATP molecule.  The new program can serve as a tool to calculate sarcomere elastic properties for any vertebrate striated muscle once various parameters have been determined (e.g. tension, T1 intercept, temperature, X-ray diffraction spacing results).

Subject Areas

myosin filament stiffness; actin filament stiffness; myosin cross-bridge stiffness; muscle transients; weak binding heads; contractile mechanism; cross-bridge cycle; rigor muscle

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