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Engineers probe mechanics behind rapid-aging disease
Date:9/14/2011

Researchers at MIT and Carnegie Mellon University are using both civil engineering and bioengineering approaches to study the behavior of a protein associated with progeria, a rare disorder in children that causes extremely rapid aging and usually ends in death from cardiovascular disease before age 16. The disease is marked by the deletion of 50 amino acids near the end of the lamin A protein, which helps support a cell's nuclear membrane.

At MIT, the researchers used molecular modeling which obeys the laws of physics at the molecular scale to simulate the behavior of the protein's tail under stress in much the same way a traditional civil engineer might test the strength of a beam: by applying pressure. In this instance, they created exact replicas of healthy and mutated lamin A protein tails, pulling on them to see how they unraveled.

"The application of engineering mechanics to understand the process of rapid aging disease may seem odd, but it actually makes a lot of sense," says Markus Buehler, a professor in MIT's Department of Civil and Environmental Engineering who also studies structural proteins found in bone and collagen. In this new research, he worked with Kris Dahl, professor of biomedical engineering and chemical engineering at Carnegie Mellon, and graduate students Zhao Qin of MIT and Agnieszka Kalinowski of Carnegie Mellon. They published their findings in the September issue of the Journal of Structural Biology.

In its natural state, a protein and its tail exist in complex folded configurations that differ for each protein type. Many misfolded proteins are associated with diseases. In molecular simulations, Qin and Buehler found that the healthy lamin A protein tail unravels sequentially along its backbone strand, one amino acid at a time.

"It behaved much as if I pulled on a loose thread on my shirt cuff and watched it pull out stitch by stitch," said Qin.

By contrast, the mutant prot
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Contact: Marta Buczek
mbuczek@mit.edu
617-721-5749
Massachusetts Institute of Technology
Source:Eurekalert

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