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Nonequilibrium, Single-Molecule Studies of Protein Unfolding Ching-Hwa Kiang, Rice University , DMR 0505814.
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Nonequilibrium, Single-Molecule Studies of Protein UnfoldingChing-Hwa Kiang, Rice University,DMR 0505814 Our group has developed a technique that can map the free energy landscapes of biomaterial interactions at the nanometer scale. Atomic force microscope is used to pull a molecule while measuring the molecule’s reaction force is measured. We have demonstrated the power of the technique in the mechanical unfolding of human cardiac titin and DNA. By quantifying the biomolecular properties, we have gained detailed knowledge about the mechanical properties of single- and double- stranded DNA. We have also studied the melting transitions of DNA-gold nanoparticles. Mismatches in DNA sequence were shown to have unexpected effects on the melting temperatures of the DNA-gold nanoparticles. The system has potential to be used as a DNA sensor. N. C. Harris, Y. Song, and C.-H. Kiang, Phys. Rev. Lett.,99, 068101 (2007). C. P. Calderon, W.-H. Chen, K.-J. Lin, N. C. Harris, and C.-H. Kiang, (2008), submitted. Studying biomaterial properties using AFM
Nonequilibrium, Single-Molecule Studies of Protein UnfoldingChing-Hwa Kiang, Rice University,DMR 0505814 Education: Five graduate (including two minority students, Nolan Harris and Eric Botello), two undergraduate (including one female) and three postdoc (including one female) worked on research supported by this NSF Award. Outreach activities include participation in high school summer academy. Students and postdoc background ranges from physics, chemistry, to bioengineering, making the research environment truly multidisciplinary. Social Impact: Single-molecule techniques allow us to probe nanoscale biomaterials properties. We developed a novel technique to study the mechanical unfolding of proteins, which will help understand the protein misfolding processes, which has been directly linked to diseases such as Alzheimer’s and Parkinson’s diseases. We have also applied the technique to study the mechanical property and melting of DNA, which is important in many diseases, ranging from virus infection to cancer. We have also examined the melting behavior of DNA-gold nanoparticle systems, and the results suggest strategies for improving the sensitivity and the accuracy of using such system as a DNA sensor. • Science News “Pulling Strings:Stretching proteins can reveal how they fold,“ 14 July 2007, Vol. 172, p.22. • APS News“Mapping Protein Folding,” March 2007, p.3. • Small Times “2007 Best of Small Tech, Researcher of the Year Award,” Vol. 8, issue 1, p. 20.