Next Article in Journal
TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy
Next Article in Special Issue
Special Issue: The Actin-Myosin Interaction in Muscle: Background and Overview
Previous Article in Journal
Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells
Previous Article in Special Issue
Insights into Actin-Myosin Interactions within Muscle from 3D Electron Microscopy
Open AccessArticle

Myosin Cross-Bridge Behaviour in Contracting Muscle—The T1 Curve of Huxley and Simmons (1971) Revisited

by Carlo Knupp 1 and John M. Squire 2,3,*
1
School of Optometry and Vision Sciences, Cardiff University, Cardiff CF10 3NB, UK
2
Muscle Contraction Group, School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol BS8 1TD, UK
3
Faculty of Medicine, Imperial College, London SW7 2BZ, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(19), 4892; https://doi.org/10.3390/ijms20194892
Received: 4 June 2019 / Revised: 26 September 2019 / Accepted: 29 September 2019 / Published: 2 October 2019
(This article belongs to the Special Issue The Actin-Myosin Interaction in Muscle)
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. Our model demonstrates that the formulations produced by previous authors give very similar results to our model if the same starting parameters are used. However, we find that it is necessary to model the X-ray diffraction data as well as mechanics data to get a reliable estimate of the cross-bridge stiffness. In the light of the high cross-bridge stiffness found in the present study, 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 may come 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 model 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). View Full-Text
Keywords: myosin filament stiffness; actin filament stiffness; myosin cross-bridge stiffness; muscle transients; weak binding heads; contractile mechanism; cross-bridge cycle; rigor muscle myosin filament stiffness; actin filament stiffness; myosin cross-bridge stiffness; muscle transients; weak binding heads; contractile mechanism; cross-bridge cycle; rigor muscle
Show Figures

Graphical abstract

MDPI and ACS Style

Knupp, C.; Squire, J.M. Myosin Cross-Bridge Behaviour in Contracting Muscle—The T1 Curve of Huxley and Simmons (1971) Revisited. Int. J. Mol. Sci. 2019, 20, 4892.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop