PHILADELPHIA Biophysicists at the University of Pennsylvania have helped develop a new technique for studying how proteins respond to physical stress and have applied it to better understand the stability-granting structures in normal and mutated red blood cells.
The research was conducted by Dennis Discher and Christine Krieger in the Molecular and Cell Biophysics Lab in Penn's School of Engineering and Applied Science, along with researchers from the New York Blood Center and the Wistar Institute.
Discher's research was published online in the journal Proceedings of the National Academy of Sciences.
In stark contrast with much of the architecture people interact with every day, the internal architecture of the human body is predominantly soft. Other than bones, all of the organs, tissues and structures in the body are pliable and flexible and need to be that way in order to work.
The Discher lab's research aims to understand what keeps these flexible structures stable, especially when they are under constant physical stress. Discher selected red blood cells as a model for this stress, as they make a complete lap of the turbulent circulatory system every few minutes but survive for months.
"Red blood cells are disks, and they have proteins right below the membrane that give it resilience, like a car tire," Discher said. "The cells are filled with hemoglobin like the tires are filled with air, but where the rubber meets the road is the exterior."
To measure stress in that membrane on an atomic level, the Discher team needed a way to track changes to the shape of those supporting proteins. They found an ideal proxy for that stress in the amino acid cysteine.
Proteins are long chain of amino acids that are tightly folded in on themselves. The order and chemical properties of the acids determine the locations of the folds, which in turn determine the function of the protein. Cysteine is "hyd
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