Influenza A virus consists of four general structures - an integral glycoprotein on the surface that guarantees entry into the host cell, a RNA-dependent RNA polymerase that later transcribes and replicates the RNA in the nucleus, eight segments of negative-sense viral RNA, and a complementary number of nucleoproteins (NP), also known as single-stranded RNA (ssRNA) binding proteins. Out of all of the components of influenza A, the nucleoproteins (NP) are a prominent factor in the life cycle of the virus. NP organizes a variety of functions that assist in the effectiveness of influenza A and is pivotal in its interactions with neighboring macromolecules from the virus and host cell. We are studying the interactions of RNP assemblies to understand the RNA transcription, replication, and packaging. The difference in free energies between ssRNA, NP, and RNP will allow use to understand the binding interactions between NP and RNA.

Von Willebrand factor (VWF) is a large glycoprotein in the blood that is responsible for blood clotting, or thrombosis, at the sites of vascular injury. To maintain hemostasis, VWF mediates platelet adhesion to the subendothelial connective tissue that lines the interior of all blood vessels and binds to the clotting factor VIII. As a glycoprotein, it can reach up to 100 micrometers in length and can exhibit tremendous flexibility in its structure. VWF function is activated by an allosteric mechanism or by high-shear induced force. Beyond the allosteric model, VWF are generally regulated by hydrodynamic forces within the blood vessels. In blood vessels, the shear rate of fluid is at its maximum near the subendothelial wall. Shear-induced adhesion enables VWF to bind to the endothelial under pathophysiological conditions and to initiate the blood clotting process at the site of vessel damage. We are studying VWF and ultra-large VWF resistance to mechanical forces and the effect of shear induced property changes. We will also study the VWF properties in the presence of ADAMTS-13 to test its reductase activity.

Kiang uses atomic force microscopy to study the protein unfolding force of single biological molecules. The development of single-molecule techniques to study protein funciton at the molecular level has expanded our understanding on the details of how biology and medicine function at the macroscopic level. Her research focuses on the mechanical properties of titin, with an emphasis on applying Jarzynski's equality to determine the free energy of titin unfolding.

Kiang's research focuses on understanding the fundamental interactions of biological molecules, including DNA, RNA, and proteins. Current research topics include porbing fundamental DNA interactions through nanogold phase transitions and single-molecule approach to studying intra- and inter- biomolecular forces.

Kiang's research focuses on understanding the interactions of biological molecules. Atomic force microscopy is used to study the forces between and within single biological molecules. The development of single-molecule techniques to studying molecular properties at the molecular level has expanded our understanding on the details of how biology and medicine function at the microscopic level. Kiang's group is studying proteins and DNA mechanics as well as developing new nanomanipulation techniques to study the properties of single-molecules.

The DNA-gold nanoparticle system is a model for phase transitions. Melting of short, free DNA is not a phase transition. However, when short DNA are bound to gold particles, the system undergoes a phase transition because the DNA-gold particles form networks of micrometer size, which is approaching a bulk phase. Thus, the binding transition in the network is much sharper than that of free DNA in solution, due to the cooperative melting process. Many fundamental aspects of phase transitions may be investigated with this biomolecular system.

We use single-molecule technique to measure the force and to determine the free energy associated with single-stranded DNA unstacking and double-stranded DNA unzipping transition. The mechanics of dsDNA separation into ssDNA are key to the DNA replication and transcription processes. DNA is highly compacted in many instances. The mechanics and energetics of bending are applicable for fabrication of artificial DNA structures, as well as providing information about the forces that must be overcome by molecular machines and motors during the packaging process of DNA into a viral capsid. We wish to determine forces and free energies of DNA stretching and unzipping, which will allow us to quantify these transitions and to obtain a physical picture of these events.

We are interested in the nucleic acid mechanical properties altered by DNA/RNA binding proteins. The change in stiffness of nucleic acids upon protein binding can be detected with single-molecule force spectroscopy. Protein binding to nucleic acids is important in many processes such as DNA repair, DNA/RNA replication, and genetic recombination. We are investigating the change in nucleic acid properties as it undergoes such transitions.

S. S. Wijeratne, J. M. Patel, and C.-H. Kiang, "Melting Transitions of DNA-Capped Gold Nanoparticle Assemblies," invited review chapter, Ann. Rev. Plasmonics (2012).

C. Guo, N. C. Harris, S. S. Wijeratne, E. W. Frey, and C.-H. Kiang, "Multiscale Mechanobiology : Mechanics at the Molecular, Cellular, and Tissue Levels," special issue on Functional
Nanomaterials, Cell & Bioscience (2012), submitted.

E. W. Frey, A. A. Gooding, S. S. Wijeratne, and C.-H. Kiang, "Understanding the Physics of DNA Using Nanoscale Single-Molecule Manipulation," Frontiers of Physics, 7 (2012) 576-581.

S. S. Wijeratne, E. Botello, H.-C. Yeh, Z. Zhou, A. Bergeron, E. W. Frey, J. M. Patel, L. Nolasco, N. Turner, J. Moake, J.-f. Dong, and C.-H. Kiang, "Mechanical Activation of a Multimeric Adhesive Protein Through Domain Conformational Change," (2012) Phys. Rev. Lett., in press.

S. S. Wijeratne, J. M. Patel, and C.-H. Kiang, "Melting Transitions of DNA-Capped Gold Nanoparticle Assemblies," Rev. Plasmonics 2010, (2012) 269-282.

W.-H. Chen, J. D. Wilson, S. S. Wijeratne, S. A. Southmayd, K.-J. Lin, and C.-H. Kiang, "Principles of Single-Molecule Manipulation and Its Application in Biological Physics," International Journal of Modern Physics B, 26 (2012) 1230006.

S. S. Wijeratne, N. C. Harris, and C.-H. Kiang, "Global and Regional Helicity Distributions of Single-Walled Carbon Nanotubes and Its Implication on the Growth Mechanism," Materials 3 (2010) 2725-2734.

W.-S. Chen, W.-H. Chen, Z. Chen, A. A. Gooding, K.-J. Lin, and C.-H. Kiang, "Direct Observation of Multiple Pathways of Single-Stranded DNA Stretching," Phys. Rev. Lett. 105 (2010) 218104.

C. P. Calderon, N. C. Harris, C.-H. Kiang, and D. D. Cox, “Analyzing
Single-Molecule Manipulation Experiments,” J. Mol. Recognit. 22 (2009) 356–362.

C. P. Calderon, N. C. Harris, C.-H. Kiang, and D. D. Cox, “Quantifying Multiscale
Noise Sources in Single-Molecule Time Series,” J. Phys. Chem. B 113 (2009) 10549–11047. Also appears on the cover page.

C. P. Calderon, W.-H. Chen, K.-J. Lin, N. C. Harris, and C.-H. Kiang, “Quantifying
DNA Melting Transitions using Single-Molecule Force Spectroscopy,” invited paper
in special issue on DNA Melting, J. Phys.: Condens. Matter 21 (2009) 034114.

E. Botello, N. C. Harris, J. Sargent, W.-H. Chen, K.-J. Lin, and C.-H. Kiang,
“Temperature and Chemical Denaturant Dependence of Forced-Unfolding of Titin
I27,” J. Phys. Chem. B 113 (2009) 10549–11047. Also appears on the cover page.

N. C. Harris and C.-H. Kiang, “Velocity Convergence of Free Energy Surfaces From
Single-Molecule Measurements Using Jarzynski’s Equality,” Phys. Rev. E 79 (2009)
041912.

S. S. Wijeratne, N. C. Harris, J. M. Cowley, and C.-H. Kiang, “Global and Regional
Helicity Distributions of Single-Walled Carbon Nanotubes and Its Implication on
the Growth Mechanism,”(2009), submitted.

"Force Measurement and Nanoparticle Aggregation for Probing Biomolecular Interactions," TAMU/Princeton Summer Workshop on Quantum Optics and Molecular Physics, Casper, WY, 16-21 July 2012.

"Force as a Probe for Detecting Dynamic States of Proteins and DNA," The Spring 2012 ACS Meeting, San Diego, CA, 25-29 March 2012.

"Single-Molecule Force Signature as a Probe for Dynamic States of DNA and Proteins," Multiscale Methods and Validation in Medicine and Biology I: Biomechanics and Mechanobiology, San Francisco, CA, 13-14 February 2012.

"Single-Molecule Manipulation and Nanoparticle Aggregation for Probing Biomolecular Interaction," Physics & Astronomy Colloquium, Texas A&M University, College Station, TX, 12 April 2012.

Direct Observation of State-to-State Transitions From Single-Molecule Manipulation Studies," In Rise of the Machines: Integration of experiment, simulation and theory for a mechanistic understanding of biomolecular machines, Telluride Science Research Center, Telluride Intermediate School, Telluride, CO, 8-12 August 2011.

"Multiple Pathways of Single-Stranded DNA Stretching Observed Using Single-Molecule Manipulation," The 2011 APS March Meeting, Dallas, TX, 21-25 March 2011.

"Observing Dynamic States of DNA and Proteins Using Single-Molecule Manipulation," invited talk at the Interdisciplinary Meeting on Mechanical Biology, Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, 17 December 2011.

"Observing Dynamic States of DNA and Proteins Using Single-Molecule Manipulation," Single Cell Biology & Real Time PCR-Boston-2011-Meeting, Waltham, MA, 4-5 April, 2011.

"Probing Dynamic States of DNA and Proteins Using Single-Molecule Manipulation," the 7th Joint Meeting of Chinese Physicists Worldwide International Conference on Physics Education and Frontier Physics (OCPA7), Kaohsiung, Taiwan, 1-5 August 2011.

"Probing Equilibrium and Dynamic States by Single-Molecule Pulling Experiments," In Single-Molecule Dynamics, Telluride Science Research Center, Telluride Intermediate School, Telluride, CO, 27 June-1 July 2011.

"Single-Molecule Approaches to Biology and Medicine," Physics & Astronomy Colloquium, Texas A&M University, Commerce, Texas, 6 October 2011.

"Single-Molecule Dynamics of DNA and Proteins," plenary talk at the 2011 Fall Joint Meeting, Texas Section of APS and AAPT, Texas A&M University, Commerce, Texas, 6-8 October 2011.

"Dynamics of Proteins and DNA From Single-Molecule Manipulation Studies," The First National Conference on Biophysical Chemistry (NCBPC1), Beijing, China, 5-7 July, 2010.

"Forces as a Probe for Dynamics of DNA and Proteins," seminar in Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China, 17 June 2010.

"Novel Conformational States of Proteins and DNA Probed by Nanomanipulation and Nanoparticle Aggregation," The Fourth Shanghai International Conference on Biophysics and Molecular Biology, Shanghai, China, 8-12 August, 2010.

"Probing Protein and DNA Interaction Forces Using Nanoparticle Aggregation and Single-Molecule Manipulation," seminar in Chemical Biology, Peking University Beijing, China, 23 March 2010.

"Probing Protein and DNA Interaction Forces Using Single-Molecule Nanobiology," The 6th Sino-US Chemistry Professors Conference, Hangzhou, China, 15-17 June 2010.

"Single-Molecule Manipulation Studies of Proteins and DNA," seminar in Institute of Physics, Chinese Academy of Sciences, Beijing, China, 22 March 2010.

"Using Mechanical Forces to Study Nano-bio Materials Properties," the 18th Annual International Conference on Composites or Nano Engineering (ICCE-18), Anchorage, Alaska, 4-10 July, 2010.

"Using Single-Molecule Manipulation to Probe Dynamic States of Proteins and DNA," seminar in Department of Photonics, National Chiao Tung University, Hsinchu, Taiwan, 23 June 2010.

"Using Single-Molecule Manipulation to Probe Dynamic States of Proteins and DNA," seminar in Institute of Physics, Academia Sinica, Taipei, Taiwan, 22 June 2010.

"Using Single-Molecule Nanomanipulation to Unravel DNA and Proteins," The 7th Cross-Strait Workshop on Biology Inspired Theoretical Science (BITS7), National Cheng-Kung University, Tainan, Taiwan, 25-30 June 2010.

“AFM Studies of the Resistance to Unfolding of Titin and von Willebrand Factor (VWF),” In session: “Track 2-2: Biological Significances of Protein Aggregation,  Folding/unfolding, and Signaling,” invited talk at the international conference BIT  Life Sciences’ 2nd annual PepCon-2009. Theme: Life, Knowledge & Bio-Economy,  Seoul, South Korea, 2–4 April 2009.

“Probing Protein and DNA Potentials with Single-Molecule Manipulation,”
Seminar in Physics, Universita di Roma “La Sapienza,” Rome, Italy, 8 June 2009.

“Protein Interaction Forces Studied with Single-Molecule Manipulation,” In session:
“Track 1-2: Proteomics and Medical Implications,” invited talk at the international
conference the 4th Medical Biotech Forum. Theme: Translating Bio-Innovations
Into Industrialization, Dalian, China, 8–10 2009.

“Seeing Biological Interactions at the Nanometer Scale,” seminar in Physics,
University of Houston-Clear Lake, Houston, TX, 2 March 2009.

“Single-Molecule Manipulation of Biological Molecules,” invited talk at the
international conference on physics education and frontier physics OCPA6,
Lanzhou, China, 3–7 August 2009.

“Single-Molecule Manipulation of DNA,” invited talk at the international
conference From DNA-inspired Physics to Physics-inspired Biology International
Center for Theoretical Physics (ICTP), Trieste-Miramare, Italy, 1–5 June 2009.

“Using Single-Molecule Manipulation to Probe the Dynamics of Protein and DNA
Molecules,” Seminar in Chemistry, University of Cambridge, Cambridge, UK, 15
June 2009.

“Using Single-Molecule Manipulation to Study Protein and Nucleic Acid
Interactions,” invited talk at the Emerging Technologies for Systems Biology, MD
Anderson Cancer Center, Houston, TX, 12 August 2009.

"Force Biomarker for Detecting Dynamic States of Proteins and DNA," keynote speech at the Biosensors & Bioelectronics-2012, Las Vegas, NV, 14-16 May 2012.

"Principles Involved in Interpreting Single-Molecule Force Measurement of Biomolecules," keynote speech at the SEM XII International Congress & Exposition on Experimental & Applied Mechanics Theme: Measurement Challenges for New Structures and Material, 13th International Symposium on MEMS and Nanotechnology, Costa Mesa, CA, 11-14 June 2012.

"Protein and DNA Interactions Studied Using Single-Molecule Manipulation," keynote speaker at the international conference BIT Life Sciences' 3nd Annual PepCon-2010, Beijing, China, 21-23 March 2010.

"Single Molecule Manipulation Methods - Atomic Force Microscope and the Applications of the Jarzynski Equality," lecture in workshop on Mechanobiology of Chromatin and Transcription, Mechanobiology Institute, National University of Singapore, Singapore, 7-10 November 2012.

“Nonequilibrium Experiments on Single Molecules,” 3 invited lectures in
Nonequilibrium Statistical Mechanics: Fundamental Problems and Applications,
2009 Boulder School for Condensed Matter and Materials Physics, Boulder, CO,
6–24 July 2009.

"Mechanical Control and Free Energy Landscapes of Single Protein and DNA Molecules," seminar in Bioengineering, California Institute of Technology, Pasadena, CA, 19 April 2012.

"Single-Molecule Force Measurements and Free Energy Landscapes of DNA and Proteins,"
seminar in Physics, University of Texas, Austin, TX, 19 March 2012.

"Exploring Biology and Medicine Through Single-Molecule Manipulation," seminar in Physics, National Taiwan University, Taipei, Taiwan, 15 December 2011.

"Observation of Misfolded Proteins and DNA Through Single Molecule Force Measurements," seminar in Institute of Physics, Academia Sinica, Taipei, Taiwan, 26 December 2011.

"Single-Molecule Investigation of Equilibrium and Dynamic Pathways of Biological Macromolecules," seminar in Chemistry, National Taiwan University, Taipei, Taiwan, ROC, 20 December 2011.

Chair for the focus session "Single Molecule Biophysics II: Novel single-molecule approaches to biology," The 2011 APS March Meeting, Dallas, TX, 21-25 March 2011.

Chair for "Session 1-4: Proteins Interacting with DNA and RNA," BIT Life Sciences' 3nd annual PepCon-2010, Beijing, China, 21-23 March 2010.