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Interplay between Viscoelasticity and Force Rate Affects Sequential Unfolding in Polyproteins Pulled at Constant Velocity.

ABSTRACT: Polyproteins are unique constructs, comprised of folded protein domains in tandem and polymeric linkers. These macromolecules perform under biological stresses by modulating their response through partial unfolding and extending. Although these unfolding events are considered independent, a history dependence of forced unfolding within polyproteins was reported. Here we measure the unfolding of single poly(I91) octamers, complemented with Brownian dynamics simulations, displaying increasing hierarchy in unfolding-foces, accompanied by a decrease in the effective stiffness. This counters the existing understanding that relates stiffness with variations in domain size and probe stiffness, which is expected to reduce the unfolding forces with every consecutive unfolding event. We utilize a simple mechanistic viscoelastic model to show that two effects are combined within a sequential forced unfolding process: the viscoelastic properties of the growing linker chain lead to a hierarchy of the unfolding events, and force-rate application governs the unfolding kinetics.

SUBMITTER: Elias-Mordechai M

PROVIDER: S-EPMC7467765 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Interplay between Viscoelasticity and Force Rate Affects Sequential Unfolding in Polyproteins Pulled at Constant Velocity.

Elias-Mordechai Moran M Chetrit Einat E Berkovich Ronen R

Macromolecules 20200414 8

Polyproteins are unique constructs, comprised of folded protein domains in tandem and polymeric linkers. These macromolecules perform under biological stresses by modulating their response through partial unfolding and extending. Although these unfolding events are considered independent, a history dependence of forced unfolding within polyproteins was reported. Here we measure the unfolding of single poly(I91) octamers, complemented with Brownian dynamics simulations, displaying increasing hier ...[more]

PMID: 32905266

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Project description:Changes in muscle shape could play an important role during contraction allowing to circumvent some limits imposed by the fascicle force-velocity (F-V) and power-velocity (P-V) relationships. Indeed, during low-force high-velocity contractions, muscle belly shortening velocity could exceed muscle fascicles shortening velocity, allowing the muscles to operate at higher F-V and P-V potentials (i.e., at a higher fraction of maximal force/power in accordance to the F-V and P-V relationships). By using an ultrafast ultrasound, we investigated the role of muscle shape changes (vastus lateralis) in determining belly gearing (muscle belly velocity/fascicle velocity) and the explosive torque during explosive dynamic contractions (EDC) at angular accelerations ranging from 1000 to 4000°.s-2. By means of ultrasound and dynamometric data, the F-V and P-V relationships both for fascicles and for the muscle belly were assessed. During EDC, fascicle velocity, belly velocity, belly gearing, and knee extensors torque data were analysed from 0 to 150 ms after torque onset; the fascicles and belly F-V and P-V potentials were thus calculated for each EDC. Absolute torque decreased as a function of angular acceleration (from 80 to 71 Nm, for EDC at 1000 and 4000°.s-1, respectively), whereas fascicle velocity and belly velocity increased with angular acceleration (P < 0.001). Belly gearing increased from 1.11 to 1.23 (or EDC at 1000 and 4000°.s-1, respectively) and was positively corelated with the changes in muscle thickness and pennation angle (the changes in latter two equally contributing to belly gearing changes). For the same amount of muscle's mechanical output (force or power), the fascicles operated at higher F-V and P-V potential than the muscle belly (e.g., P-V potential from 0.70 to 0.56 for fascicles and from 0.65 to 0.41 for the muscle belly, respectively). The present results experimentally demonstrate that belly gearing could play an important role during explosive contractions, accommodating the largest part of changes in contraction velocity and allowing the fascicle to operate at higher F-V and P-V potentials.

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Interplay between Viscoelasticity and Force Rate Affects Sequential Unfolding in Polyproteins Pulled at Constant Velocity.

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Interplay between Viscoelasticity and Force Rate Affects Sequential Unfolding in Polyproteins Pulled at Constant Velocity.

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