Protein 'sacrifice' spares bones

SANTA BARBARA, Calif., Dec. 12 (UPI) -- Bones can take a beating because of "sacrificial" bonds of chemical compounds which absorb bumps, jolts and stretches that otherwise could cause injury, researchers have found.

Such protective altruism empowers the bone to withstand the impacts without weakening, though it is not impervious to all forces and does fracture or break under severe pressure, the scientists from the University of California, Santa Barbara, reported in the British journal Nature.

The toughness against minor pounding is as much a hallmark of bone as is the stiffness that provides solid skeletal support, investigators said. While scientists have a good grasp on the mechanisms underlying bone rigidity, produced by pervasive microscopic mineral crystals, their insight into what lies beneath its toughness has been sketchy.

To clarify the picture, physicist James Thompson and his colleagues studied the response of rat and bovine bone to pulling, using an atomic force microscope, an instrument originally developed to produce minutely detailed surface images, but which also can be used to stretch single protein molecules, such as collagen. The protein is found in skin, ligaments, tendons, bone, cartilage and other connective tissue.

"The protein is stretched by a diamond on the end of a cantilever so that the force required, and the distance that the protein is stretched, can be measured," explained biologist John Currey of the University of York in England, who analyzed the findings in an accompanying commentary. "The diamond can be pressed into the surface of hard materials such as bone, and the force of the elastic recoil can be measured to determine the mechanical properties at that point in the surface."

Thompson and crew found the time it took bone to recover from the pulling correlated with the time it took the protective bonds that shattered in absorbing the shock to regroup.

The study suggests "collagen -- the main organic constituent of bone -- has 'sacrificial bonds' that are broken upon loading without significantly harming the bone," Currey said. "Bone's toughness comes from the mechanical work required to overcome these bonds. Some of these sacrificial bonds reform when the force is removed, allowing bone to repair itself to some extent.

"It is a new suggestion about how bone manages to be reasonably tough, which is a bit of a mystery at the moment," Currey told United Press International.

The bonds are not omnipotent, and there comes a point at which the mechanism no longer comes into play, the impact being severe enough to result in a fracture or break.

In such cases, "they just break up entirely, and then all hell gets loose biologically, and this particular mechanism is irrelevant," Currey said.

Here, the polymers would likely sustain permanent damage.

"Your body has a mechanism, called remodeling, to remove damaged portions of your bones and replace them. The role of collagen may well be to help prevent such serious injuries from occurring," Thompson told UPI.

Bone, the hard tissue that forms the body's skeleton in vertebrate animals, is a mixture of mineral crystals which, if not for the sacrificial bonds, would be brittle and prone to fracture, the investigators found. Each time a bond shatters, others come to the rescue, multiplying by hundreds or thousands the energy needed to break the entire collagen molecule. The collagen fibers and adjacent calcium salt crystals that comprise bone possess the strength of reinforced concrete.

In the very young, the skeleton is composed largely of pliable cartilage, reducing the risk of bone breaks. As the body gets older, decreases in bone mass may lead to higher vulnerability to fracture.

The bonds may play some part in the changes bones undergo as they age or are beset by such disorders as osteoporosis, researchers told UPI.

"It is known that older people's collagen in bone is not as 'good' as younger people's, and the bone is less tough. There is some (not very clear) evidence that osteoporotic bone collagen is different from that of bone of relatively healthy people of the same age," Currey told UPI.

In their study, Thompson and team repeatedly stretched collagen molecules between a surface and the tip of an atomic force microscope.

"From these experiments, we learn how much force it takes to stretch a collagen molecule. We found that bonds within or between these molecules rupture as they are stretched, but these bonds reform if the molecules are allowed to 'rest' for about 30 seconds between stretching cycles," Thompson said. "We also observed that bone recovers from microscopic indentations in a similar 30-second time period, which suggests the rupture and reformation of bonds in collagen may be important to the mechanical properties of bone."

The findings have been long in coming.

"Despite centuries of work, dating back to Galileo (an Italian physicist and astronomer who lived from 1564 to 1642), the molecular basis of bone's toughness and strength remains largely a mystery," Thompson said. "A great deal is known about bone microstructure and the microcracks that are precursors to its fracture, but little is known about the basic mechanism for dissipating the energy of an impact to keep the bone from fracturing."

"These studies are aimed at developing a fundamental understanding of bone strength," Thompson told UPI.

From the experiments with cow and rat femurs, the longest, largest, strongest of all bones, the team found that bone, like abalone mother-of-pearl, contains chemical compounds whose bonds both protect the backbone of the polymer and dissipate potentially damaging energy.

The findings should apply to all human bones, perhaps even to dentin in teeth, Currey said.

"Collagen is the single most common protein in the human body and makes up a significant fraction of the mass of a human bone. Further, although there are significant differences in the bones of cows, rats and humans, at small size scales, all three are largely composed of mineralized collagen fibers," Thompson said.

While the findings "are potentially important" for understanding the behavior of bone under pressure, "there is still a considerable element of speculation in all this," Currey cautioned.

"It may be, if we know the real origin of bone toughness, and if we could find ways of preventing it changing with age, it would keep bones tougher with aging. That's a big 'if' however," he told UPI. "If we could manipulate these collagen bonds, it would be wonderful. It will, however, be extremely difficult."