Key result
In silico modeling of a virtual half sarcomere structure confirmed that the T1 curve comes almost entirely from length changes in the myosin and actin filaments.
Why the study?
Myosin cross-bridge stiffness is key to understanding force generation, but evidence showed filament compliance contributes significantly to sarcomere elasticity, challenging earlier models attributing compliance mainly to myosin heads.
In silico modeling suggests that most of the instantaneous T1 response in active muscle comes from filament compliances and weakly-bound myosin heads, rather than strongly attached states.
Supports filament compliance models; leaves open experimental validation in intact cardiac 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. 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).
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Knupp et al. (2019) studied Muscle contraction. In silico modeling of virtual half sarcomere structure was evaluated on Cross-bridge stiffness and contribution to T1 curve. In silico modeling of a virtual half sarcomere structure confirmed that the T1 curve comes almost entirely from length changes in the myosin and actin filaments.
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