How the ‘building blocks’ of muscles work together

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Researchers have examined closely how sarcomeres, the basic building blocks within all skeletal and cardiac muscles, work together using a new technique.

Their findings could advance research into a wide range of muscle malfunctions as simple as a slight strain after exercise or as serious as heart failure and muscular dystrophy.

Sarcomeres are the smallest unit within a muscle in which all the molecules responsible for making a muscle work can be found intact. These minuscule structures, about one hundred times smaller in diameter than an average human hair, work cooperatively to produce force during muscle contraction.

Scientists have known for some time that when muscles are active, many million sarcomeres work together, and that muscle malfunctions can be due, at least in part, to miscommunication between sarcomeres. But how exactly this communication takes place has been a mystery until now. No one before has been able to isolate a single sarcomere, watch it in action, and measure what’s going on.

“It was very, very tricky and sometimes frustrating for the students working on this project over the last few years,” says Dilson Rassier, who teaches in the kinesiology department at McGill University and is the lead researcher on the study in the Proceedings of the National Academy of Sciences.

“We used micro-fabricated needles to measure force and high-tech microscopy to isolate the sarcomeres and then watch them contracting. One of our collaborators had to develop a mathematical model to analyze the data because the numbers involved were so minuscule and so precise,” Rassier says.

There are between 2,000 and 2,500 sarcomeres found together in linked coils in each 10 millimeters of muscle fiber. To watch the sarcomeres in action, the researchers first had to isolate a single myofibril (the basic rod-like units which make up muscle tissue) and then zoom in on an individual sarcomere. Then they experimented with different concentrations of calcium (which is responsible for triggering muscle activation and relaxation) to cause the sarcomeres to contract and measure their force.

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They discovered that, in a healthy myofibril, all the neighboring sarcomeres adjust to the activation of one single sarcomere.

This finding shows a cooperative mechanism among sarcomeres in a myofibril that is linked to the specific properties of sarcomeric molecules. This inter-sarcomere dynamic is crucial for the understanding of the molecular mechanism of contraction.

“Our next step is to look into what happens in heart failure and other diseases of the muscular system when sarcomeres fail to cooperate,” says Rassier.

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The Canadian Institutes for Health Research (CIHR), the Natural Science and Engineering Research Council of Canada (NSERC), the National Counsel of Technological and Scientific Development (CNPq, Brazil), and the Canada Research Chair Program provided funding for the study.

Source: McGill University