Astronauts returning from a bout of weightlessness experience painful tearing of muscle cells when they set foot on Earth.

But much like a punctured tire is patched, muscles cells literally ripped apart by use after even a week of disuse appear to patch themselves in a matter of seconds, according to researchers at the Medical College of Georgia.

“Nature has retained the economy of the patch,” said Dr. Paul L. McNeil, cell biologist. “In nature, cells repair surface tears much like a mechanic used to repair a flat, by applying a membrane patch to the torn spot.”

Dr. McNeil first identified this patching process in some of life’s simplest forms: sea urchin eggs and fibroblasts. Now, with funding from the National Aeronautics and Space Administration, he’s determining if the process holds up in more complex life forms.

“In space, none of the major muscle groups, the legs, hips and back, are loaded under gravity,” Dr. McNeil said. “You can move yourself from one end of the spaceship to the other by just pushing on something with your little finger.”

But soft muscle tissue adapts to its environment; rather than increasing in number, these cells increase in size in response to mechanical load. “You remove load from the muscle and it shrinks,” Dr. McNeil said. “That’s an unfortunate fact of life. None of us is going to look like Arnold Schwartznegger unless we exercise like him.”

Weightless life in space is more akin to time spent as a couch potato. When astronauts return and reload muscles B particularly with activities, such as walking down stairs or down a hill, that simultaneously stretch and contract muscles, the result is microscopic tears in the membrane of the muscle cells.

Dr. McNeil suspects that the muscle soreness athletes experience is probably a consequence of this tearing; that tearing triggers an inflammatory response directly responsible for the pain. Excessive cell tearing also is a factor in the progressive, debilitating disease Duchenne’s muscular dystrophy, he said.

“The cells lose their all-important external boundaries,” Dr. McNeil said. The result is that calcium B present outside these cells at concentrations10,000 times higher than intracellular levels B rushes in to promote healing or wreak destruction.

“It’s a paradox,” Dr. McNeil said. Inside muscle cells, the normal, low levels of calcium signal muscle contraction. In studies first done in sea urchins and fibroblasts, Dr. McNeil documented that when extracellular calcium rushes in through a tear in the cell membrane, it can either help form the cell-saving patch or destroy the cell, possibly by prompting the cell to contract to death.

“In a sea urchin egg, you can rip off 1,000 square microns of surface, the equivalent of one-third of the surface of the egg and, within seconds, no more calcium is coming in,” Dr. McNeil said. “There is complete restoration of the surface covering of the egg within seconds.

The egg can then be fertilized and go on to divide; so afterward, it’s healthy,” he said of research findings first published in Journal of Cell Biology and Journal of Cell Science; a review article is scheduled for the May issue of Nature Cell Biology.

The cell-saving patch results from a fusion of vesicles, little spherical structures that normally nourish the cell, and the initial onslaught of external calcium. “The calcium that rushes in through the membrane disruption causes small vesicles or membranes inside the cells, to fuse with each other, making a bigger membrane structure that is a patch,” Dr. McNeil said. “The patch then fuses with the cell surface.”

But if that patch doesn’t form, calcium continues to rush in, rapidly becoming the villain by killing off some of the finite number of muscle cells. “If you inhibit this (patching) process, within less than a minute, the cell will be dead,” Dr. McNeil said.

With the three-year, nearly $900,000 grant from NASA, Dr. McNeil is using a laser to simulate in a mouse model the tearing that occurs when an astronaut reacquaints with gravity, then documenting the repair process.

“If we can understand at the molecular level how this resealing occurs, we might be able to promote it and, in the case of astronauts or trauma victims or other people with massive muscle damage, we might be able to facilitate the repair or healing process,” Dr. McNeil said.

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Contact: Toni Baker
tbaker@mail.mcg.edu
706-721-4421
Medical College of Georgia