Preventing the Unfolding of Proteins: Covalently Bonded Polymers Can Theoretically Stabilize Small Proteins

When the body loses its ability to fold proteins into the correct shapes, the result can be irreversible and tragic. The accumulation of unfolded or misfolded proteins in the brain causes many devastating neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS) (Lou Gehrig’s disease). In order to maintain their functions, structural proteins and engineered, protein-based materials need to avoid unfolding even under large mechanical stresses. Scientists, therefore, are exploring ways to design proteins that can survive extreme mechanical insults. Now, Northwestern Engineering's Sinan Keten has theoretically demonstrated that small proteins can be reinforced with covalently bonded polymers against mechanical unfolding. His computational model illustrates strategies for using this polymer conjugation to prevent proteins from rapidly unfolding even when stretched or pulled. "If you apply a stress to a protein, we know it will start to unfold," said Dr. Keten, Assistant Professor of Mechanical, Civil, and Environmental Engineering at Northwestern. "Given that proteins are subject to mechanical forces in the body and in all applications, it will be useful to reinforce them in this way." Dr. Keten's research is featured on the cover of the February issue of the journal ACS Nano. Elizabeth DeBenedictis, a Ph.D. student in Keten's lab, and Elham Hamed, Ph.D., a former postdoctoral fellow in Keten's lab, are the paper's first authors. DeBenedictis also created the diagram that was used for the journal's cover image. The ACS Nano article is titled “Mechanical Reinforcement of Proteins with Polymer Conjugation.”
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