AsianScientist (Oct. 26, 2017) – In a study published in Nature Communications, scientists in Japan have discovered how the skeletal muscle protein, myosin, works collectively to generate force in response to heavy loads.
Skeletal muscles are critical for carrying out a wide range of biological functions, from moving the body, to eye movements that adjusting our vision and focus, to tongue motions involved in speech. Muscle contraction is driven by myosins, which form a myofilament—an ultramicroscopic ensemble comprising approximately 300 molecules interacting with filaments of actin, another muscle protein.
“I find it intriguing that muscles that make it possible to run at full speed or those that move the crystalline lens in the eyeball are essentially the same, sharing identical structures. In my research, I have been looking for the answer to reveal its molecular mechanism,” said study co-author Assistant Professor Motoshi Kaya of the University of Tokyo.
In this study, the group of researchers led by Professor Hideo Higuchi at the Graduate School of Science at the University of Tokyo set out to answer the question of whether specific molecular properties give rise to myosins’ collective generation of force.
The researchers measured the forces and movements of skeletal myosins by producing synthetic myofilaments made up of approximately 20 molecules, which interact with a single actin filament. They then assessed the motion of beads 400 nanometers (nm) in diameter, which they placed on the actin. This allowed them to perform the first-ever measurement of approximately 5 nm stepwise displacements of actin at the physiologically relevant concentration of ATP, a compound that serves as a source of energy.
Thermodynamically, only the coordinated actions of multiple myosins would be able to generate the steps observed in response to higher loads. To shed light on this phenomenon, the group developed a model simulating the coupling effect of multiple myosins. They revealed that the muscle proteins can increase the probability of generating collective force if each molecule remains on standby, and thus cooperates to produce force, like a tug-of-war team.
The study’s findings propose a new principle of efficient force generation among myosin molecules, which intrinsically function randomly, but become cooperative by sensing an increase in load.
“I thought the stepwise actin displacements against such high loads were only possible if myosins somehow generated force synchronously. We were able to gain a clear understanding of the coordinated force generation among myosin motors based on our experimental data and simulation model,” said Higuchi.
The current findings may contribute to the development of efficient nanomachines and artificial actuators—mechanisms that convert energy into motion—in the future.
The article can be found at: Kaya et al. (2017) Coordinated Force Generation of Skeletal Myosins in Myofilaments through Motor Coupling.
Source: University of Tokyo; Photo: Shutterstock.
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