Stultz, team reveal bad/good cop role of collagen

May 14, 2010

MIT associate professor Collin Stultz, a cardiologist and biomedical engineer, studies the structure of collagen.  Photo: Patrick Gillooly

Collin Stultz, the W. M. Keck Associate Professor of Biomedical Engineering in the EECS Department and HST (Health Sciences and Technology) and a board certified internist and cardiologist and principal researcher in the Research Lab of Electronics at MIT (RLE) has been interested in understanding collagen, a pervasive connective tissue comprising 30% of the human body for a long time.

As noted today, May 14, in an MIT News Office article about Stultz's work, when cholesterol builds up in the arteries, giving rise to plaques, collagen forms a protective layer that envelops the plaques. If collagen fails to hold the plaques together, they burst, spilling out cholesterol, other fatty molecules, and blood-clotting agents — usually with disastrous consequences.

“Catastrophic heart attacks — the kind where you’re walking down the street, or watching TV, and then keel over and die — are most often associated with a rupture of the collagen layer,” Stultz told the MIT News Office.

In fact, Stultz has published a series of papers that have helped transform the prevailing theories on collagen, which has traditionally been thought of as a rigid, rope-like molecule. In his most recent paper, published online in the journal Biochemistry last month, Stultz and his colleagues showed that, depending on the temperature, collagen can switch between its usual rigid structure and a much floppier, more flexible shape.

For the past couple of decades, scientists have been trying to figure out the relationship between collagen and the enzymes, known as collagenases, that break it down in the body. Because collagen is a critical component of so many structural elements, such as bone and skin, its degradation is very carefully controlled.

Structural studies that require crystallizing the protein (a common technique also used to reveal the double helix structure of DNA) showed that collagen is a tightly wound triple helix. However, that structure puzzled scientists because it offers no access for collagenase enzymes to bind to and break down the protein. “If you just look at the structures, you would say collagen should never be broken up by these enzymes,” says Stultz.

Stultz suspected that the low temperatures (10 degrees Celsius) required to crystallize collagen in those studies might be masking some aspect of the protein’s true structure. He did computer modeling that suggested higher temperatures, such as room or body temperature, allow some sections of the collagen molecule to unwind, becoming floppy. That structure also opens up a site that fits collagenase perfectly, allowing it to break down the protein.

“We think of collagen as being a very rigid molecule, while in practice there may be regions of collagen that are very floppy and loose,” says Stultz.

Read more:

Biochemistry April 15, 2010 article "Cleavage Site Specificity and Conformational Selection in Type I Collagen Degradation"

Other reported work of Collin Stultz, MIT News Office April 21, 2008 "MIT zeroes in on Alzheimer's structures"