A myosin II nanomachine mimicking the striated muscle

Irene Pertici,Luca Salvi,Giulio Bianchi,Pasquale Bianco,Dan Cojoc,Caterina Squarci,Miklós S Z Kellermayer,Giulia Falorsi,Luca Melli,Tamás Bozó,Vincenzo Lombardi,Lorenzo Bongini

doi:10.1038/s41467-018-06073-9

Abstract

The contraction of striated muscle (skeletal and cardiac muscle) is generated by ATP-dependent interactions between the molecular motor myosin II and the actin filament. The myosin motors are mechanically coupled along the thick filament in a geometry not achievable by single-molecule experiments. Here we show that a synthetic one-dimensional nanomachine, comprising fewer than ten myosin II dimers purified from rabbit psoas, performs isometric and isotonic contractions at 2 mM ATP, delivering a maximum power of 5 aW. The results are explained with a kinetic model fitted to the performance of mammalian skeletal muscle, showing that the condition for the motor coordination that maximises the efficiency in striated muscle is a minimum of 32 myosin heads sharing a common mechanical ground. The nanomachine offers a powerful tool for investigating muscle contractile-protein physiology, pathology and pharmacology without the potentially disturbing effects of the cytoskeletal—and regulatory—protein environment.

Highlights

The contraction of striated muscle is generated by ATPdependent interactions between the molecular motor myosin II and the actin filament
The motors of each half thick filament are mechanically coupled via the thick filament backbone, which allows for steady contraction in spite of the fact that the individual myosin heads interact with actin only briefly and remain detached throughout most of their ATP hydrolysis cycle
The nanomachine is an ensemble of fast vertebrate skeletal-muscle heavy meromyosin (HMM) molecules attached onto a singlemode optical fibre chemically etched to a diameter of ~4 μm

Summary

Introduction

The contraction of striated muscle (skeletal and cardiac muscle) is generated by ATPdependent interactions between the molecular motor myosin II and the actin filament. The motors of each half thick filament are mechanically coupled via the thick filament backbone, which allows for steady contraction in spite of the fact that the individual myosin heads interact with actin only briefly and remain detached throughout most of their ATP hydrolysis cycle. To attain the efficiency of striated muscle with a one-dimensional machine, a minimum of 32 myosin heads sharing a common mechanical ground must be available for interaction with the actin filament

Methods

Results

Conclusion