Scientists have genetically engineered muscles to move in response to pulses of light.
The technique, demonstrated on vocal cords removed from mice, is reported on 2 June in Nature Communications1. Researchers say that it could probe how muscles function — and might eventually help to treat people who have a paralysis that interferes with speech and breathing.
The work relies on a method called optogenetics, which can make cells that usually respond to electrical signals also react to light. The approach alters mammalian cells by inserting a gene for a protein such as channelrhodopsin, which in its natural setting allows blue-green algae to swim towards or away from light.
Optogenetics was first used in 2005 to modify neurons2, and has since become a standard tool to study the brain and nervous system. Applications outside neuroscience, however, are less common.
The latest study is fascinating, says Julio Vergara, a physiologist at the University of California, Los Angeles, who studies how electrical signals cause muscles to contract. “It shows the potential use of this very powerful technique for very important medical problems,” he says.
The study's authors had previously used optogenetics to engineer heart muscle in mice3 — light caused parts of the heart to beat out of sync, simulating arrhythmias. The latest research extends this to muscles that move under conscious command.
“Skeletal muscles follow different rules than the heart,” says Philipp Sasse, a co-author of the study and a physiologist at the University of Bonn in Germany. “Each fibre in a skeletal muscle can contract separately, which allows controlling movements as well as muscle strength very precisely.”
Flip the switch
Sasse and his colleagues engineered mice so that their muscles would produce channelrhodopsin. The researchers were forced to test their method on dissected organs because there was no way to position a light source properly in a live mouse.
The idea to work on the larynx came from one of Sasse’s co-authors, who had learned about laryngeal paralysis while on an internship with physicians who treat ear, nose and throat disorders. Such paralysis, which can result from thyroid operations and nerve conditions, prevents muscles in the larynx from moving apart when a person breathes.
Therapies that treat laryngeal disease with electrical stimulation are ineffective, says Sasse. Muscle fibres that open and close the airway lie so close together that electrodes cannot stimulate one without also stimulating the other, unless the constricting muscles are first immobilized with botulinum toxin. Implanted electrodes can also degrade quickly, and they are often uncomfortable.
Stimulating muscle fibres with light offers more precise control, the latest study finds. In principle, optogenetics could one day be used to treat a variety of movement disorders, Vergara says. In many diseases, the nerves degrade but the muscles remain viable. “Anything that can stabilize the muscle could bring the possibility of treatment,” he says.
Optogenetics also could help to reveal basic details about muscle physiology. These include how electrical signals produce muscle contractions; many laboratory experiments require researchers to apply external electrical stimuli to muscle cells, confounding results. Harnessing light to produce muscle contractions could eliminate that problem, Vergara says.
Sasse and his colleagues hope to try their method next year in live pigs — test subjects that offer several advantages over mice. A pig's trachea is larger than that of a mouse, and closer in shape and size to that of a person. A light-emitting device suitable for pigs would also probably work in humans, Sasse says.
But, he adds, any test of the technique in humans would require researchers to figure out how to safely and efficiently introduce the channelrhodopsin gene into muscle cells.
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