Minimally invasive high-speed imaging of sarcomere contractile dynamics in mice and humans

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Abstract
Sarcomeres are the basic contractile units of striated muscle. Uncovering how sarcomeres change length and develop force is fundamental to understanding biomechanics, muscle physiology, and neuromuscular control. Llewellyn et al. describe the use of optical microendoscopy to visualize sarcomeres and their micrometre-scale motions in live mice and humans, revealing unanticipated local variations in sarcomere lengths. Imaging of human sarcomeres is expected to enable advances in biomechanical modelling, orthopaedic therapeutics, and the understanding and treatment of neuromuscular disorders. This paper describes the use of optical microendoscopy to visualize sarcomeres and their micron-scale motions in live mice and humans, revealing unanticipated local variations in sarcomere lengths. Imaging of human sarcomeres is expected to enable advances in biomechanical modelling, orthopedic therapeutics, and the understanding and treatment of neuromuscular disorders Sarcomeres are the basic contractile units of striated muscle. Our knowledge about sarcomere dynamics has primarily come from in vitro studies of muscle fibres1 and analysis of optical diffraction patterns obtained from living muscles2,3. Both approaches involve highly invasive procedures and neither allows examination of individual sarcomeres in live subjects. Here we report direct visualization of individual sarcomeres and their dynamical length variations using minimally invasive optical microendoscopy4 to observe second-harmonic frequencies of light generated in the muscle fibres5,6 of live mice and humans. Using microendoscopes as small as 350 μm in diameter, we imaged individual sarcomeres in both passive and activated muscle. Our measurements permit in vivo characterization of sarcomere length changes that occur with alterations in body posture and visualization of local variations in sarcomere length not apparent in aggregate length determinations. High-speed data acquisition enabled observation of sarcomere contractile dynamics with millisecond-scale resolution. These experiments point the way to in vivo imaging studies demonstrating how sarcomere performance varies with physical conditioning and physiological state, as well as imaging diagnostics revealing how neuromuscular diseases affect contractile dynamics.