Hongbin Li

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Hongbin Li

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Research and Teaching Interests

Single molecule biophysical chemistry, biomaterials, polymer chemistry, biological chemistry

2017: Multiple graduate student positions available

 

Our research program is in the area of single molecule biophysical chemistry. We are interested in the mechanical properties and conformational dynamics of elastic proteins. Elastic proteins are important structural and functional components in living cells. They serve as molecular springs in tissues to establish elastic connections and provide mechanical strength, elasticity, and extensibility. They are not only important for their biological functions in various biological processes, but also important building blocks for bottom-up construction of smart materials and mechanical devices on the nanoscale.

Our main research tool is single molecule atomic force microscopy. The AFM is a powerful technique allowing us to directly manipulate proteins one molecule at a time. We use the AFM to measure the mechanical properties of proteins, and monitor the folding/unfolding trajectories of single protein in real time. Our long term goal is to understand the mechanical properties of proteins at the single molecule level and use protein engineering techniques to design proteins with tailored mechanical properties to be used as functional and structural components for smart materials and nanomechanical devices.

 

 

Research directions

1. Protein Mechanics and Engineering: combining protein engineering with single molecule AFM and computation, we rationally design and engineer proteins with tailored mechanical properties.

Representative publications: 

J. Am. Chem. Soc.  2012, 134, 4124-4131.
Acc. Chem. Res. 201043, 1331-1341.
J. Am. Chem. Soc. 2009131,14050-14056.
Proc. Nat. Acad. Sci. USA, 2008, 105, 11152-11157.
Nature Nanotechnology, 2008, 3, 512-516.

 

2. Single Protein Folding/Unfolding Dynamics: we use single molecule force spectroscopy techniques to investigate the folding/unfolding dynamics and mechanism of proteins at the single molecule level.

Representative publications:

Proc. Nat. Acad. Sci. USA, 2013110, 18156-18161.
J. Am. Chem. Soc. 2013135, 7992-8000.
BIOPHYSICAL JOURNAL 2012103, 807-816.
J. Am. Chem. Soc. 2012134, 10428-10435.
J. Am. Chem. Soc. 2009, 131, 13347-13354.
Proc. Nat. Acad. Sci. USA, 2008, 105, 1885-1890.

 

3. Protein-based Biomaterials: using the knowledge from protein mechanics studies, we rationally design protein-based biomaterials with tailored mechanical properties for various biomedical applications. We rationally tailor macroscopic mechanical properties of these biomaterials by programming the molecular sequence, and thus nanomechanical properties, of protein building blocks at the single-molecule level.

Representative publications: 

Nature 2010, 465, 69 – 73.
Nature Communications 2013, 4.
Acta Biomaterialia 2013, 9, 6481-6491.
Langmuir 2012, 28, 2269-2274
Chem. Commun. 2008, 4144-4146.

 

4. Polymer physical chemistry using single molecule AFM: we use single molecule AFM to investigate the conformational change of polymers at the singel molecule level. 

5. AFM imaing of biological materials

 

 

Contact

Real name: 
Email: 
Office Room Number(s): 
Chemistry A247
Office Phone Number: 
604-822-9669
Fax Number: 
604-822-2847

Curriculum Vitae

Professional
  • 2013-present    Professor and Canada Research Chair (University of British Columbia)
  • 2009-2013         Associate Professor and Canada Research Chair (University of British Columbia)
  • 2004-2009         Assistant Professor and Canada Research Chair(University of British Columbia)
  • 2002-2004         Associate Research Scientist (Columbia University, USA)
Education
  • 1999-2002     Research Fellow (Mayo Medical Center, USA, Advisor: Prof. Julio M. Fernandez)
  • 1993-1998     Ph.D. (Polymer Chemistry and Physics at Jilin University, China, Advisors: Profs. Jiacong Shen, Xi Zhang and Hermann E. Gaub)
  • 1996-1997     Visiting PhD student (Ludwig-Maximilians-Universität München, Germany, Advisor: Prof. Hermann E. Gaub)
  • ​1989-1993     B.Sc (Polymer Engineering, Tianjin University, China)
Awards
  • 2012   Changjiang Guest Chair Professorship (Jilin University, China)
  • 2011   JILA Visiting Fellowship (JILA and University of Colorado, Boulder)
  • 2011   Alexander von Humboldt Fellowship (Technical University of Munich, Germany)
  • 2010   JILA Distinguished Short-term Visiting Fellow (JILA and University of Colorado, Boulder)
  • 2010   Charles McDowell Award for Research (UBC)
  • 2006   Michael Smith Foundation for Health Research Career Investigator Award
  • 2005   Peter Wall Institute for Advanced Studies Early Career Award (UBC)

Publications

In Press

Kong, N. ; Fu, L. ; Peng, Q. ; Li, H. Metal Chelation Dynamically Regulates The Mechanical Properties Of Engineered Protein Hydrogels. ACS Biomaterials Science & Engineering In Press.

2016

Gao, X. ; Fang, J. ; Xue, B. ; Fu, L. ; Li, H. Engineering Protein Hydrogels Using Spycatcher-Spytag Chemistry. BIOMACROMOLECULES 2016, 17, 2812-2819.
Li, H. ; Kong, N. ; Laver, B. ; Liu, J. Hydrogels Constructed From Engineered Proteins. SMALL 2016, 12, 973-987.
Si, C. ; Li, J. ; Luo, Q. ; Hou, C. ; Pan, T. ; Li, H. ; Liu, J. An Ion Signal Responsive Dynamic Protein Nano-Spring Constructed By High Ordered Host-Guest Recognition. CHEMICAL COMMUNICATIONS 2016, 52, 2924-2927.
Feng, J. ; Lamour, G. ; Xue, R. ; Mirvakliki, M. Negar; Hatzikiriakos, S. G. ; Xu, J. ; Li, H. ; Wang, S. ; Lu, X. Chemical, Physical And Morphological Properties Of Bacterial Biofilms Affect Survival Of Encased Campylobacter Jejuni F38011 Under Aerobic Stress. INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY 2016, 238, 172-182.

2015

Lei, H. ; Hu, X. ; Zhu, P. ; Chang, X. ; Zeng, Y. ; Hu, C. ; Li, H. ; Hu, X. Nano-Level Position Resolution For Particle Tracking In Digital In-Line Holographic Microscopy. Journal of Microscopy 2015, 260, 106.
Kong, N. ; Li, H. Protein Fragment Reconstitution As A Driving Force For Self-Assembling Reversible Protein Hydrogels. ADVANCED FUNCTIONAL MATERIALS 2015, 25, 5593-5601.
Panwar, P. ; Lamour, G. ; Mackenzie, N. C. W. ; Yang, H. ; Ko, F. ; Li, H. ; Broemme, D. Changes In Structural-Mechanical Properties And Degradability Of Collagen During Aging-Associated Modifications. JOURNAL OF BIOLOGICAL CHEMISTRY 2015, 290, 23291-23306.
He, C. ; Hu, C. ; Hu, X. ; Hu, X. ; Xiao, A. ; Perkins, T. T. ; Li, H. Direct Observation Of The Reversible Two-State Unfolding And Refolding Of An Alpha/beta Protein By Single-Molecule Atomic Force Microscopy. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2015, 54, 9921-9925.
Zheng, P. ; Arantes, G. M. ; Field, M. J. ; Li, H. Force-Induced Chemical Reactions On The Metal Centre In A Single Metalloprotein Molecule. NATURE COMMUNICATIONS 2015, 6, 7569.
Hu, C. ; An, R. ; Zhang, C. ; Lei, H. ; Hu, X. ; Li, H. ; Hu, X. Design Of A High-Quality Optical Conjugate Structure In Optical Tweezers. APPLIED OPTICS 2015, 54, 1410-1413.

2014

Zheng, P. ; Wang, Y. ; Li, H. Reversible Unfolding-Refolding Of Rubredoxin: A Single-Molecule Force Spectroscopy Study. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2014, 53, 14060-14063.
Kong, N. ; Peng, Q. ; Li, H. Rationally Designed Dynamic Protein Hydrogels With Reversibly Tunable Mechanical Properties. ADVANCED FUNCTIONAL MATERIALS 2014, 24, 7310-7317.
Kovacic, S. ; Samii, L. ; Lamour, G. ; Li, H. ; Linke, H. ; Bromley, E. H. C. ; Woolfson, D. N. ; Curmi, P. M. G. ; Forde, N. R. Construction And Characterization Of Kilobasepair Densely Labeled Peptide-Dna. BIOMACROMOLECULES 2014, 15, 4065-4072.
He, C. ; Lamour, G. ; Xiao, A. ; Gsponer, J. ; Li, H. Mechanically Tightening A Protein Slipknot Into A Trefoil Knot. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2014, 136, 11946-11955.
Xue, Y. ; Li, X. ; Li, H. ; Zhang, W. Quantifying Thiol-Gold Interactions Towards The Efficient Strength Control. NATURE COMMUNICATIONS 2014, 5, 4348.
Bull, M. S. ; Sullan, R. May A. ; Li, H. ; Perkins, T. T. Improved Single Molecule Force Spectroscopy Using Micromachined Cantilevers. ACS NANO 2014, 8, 4984-4995.
Wang, Y. ; Hu, X. ; Bu, T. ; Hu, C. ; Hu, X. ; Li, H. Molecular Calipers For Highly Precise And Accurate Measurements Of Single-Protein Mechanics. LANGMUIR 2014, 30, 2761-2767.

2013

Fang, J. ; Mehlich, A. ; Koga, N. ; Huang, J. ; Koga, R. ; Gao, X. ; Hu, C. ; Jin, C. ; Rief, M. ; Kast, J. ; Baker, D. ; Li, H. Forced Protein Unfolding Leads To Highly Elastic And Tough Protein Hydrogels. Nature Communications 2013, 4.
Zoldak, G. ; Stigler, J. ; Pelz, B. ; Li, H. ; Rief, M. Ultrafast Folding Kinetics And Cooperativity Of Villin Headpiece In Single-Molecule Force Spectroscopy. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2013, 110, 18156-18161.
Ostapchenko, V. G. ; Beraldo, F. H. ; Mohammad, A. H. ; Xie, Y. - F. ; Hirata, P. H. F. ; Magalhaes, A. C. ; Lamour, G. ; Li, H. ; Maciejewski, A. ; Belrose, J. C. ; Teixeira, B. L. ; Fahnestock, M. ; Ferreira, S. T. ; Cashman, N. R. ; Hajj, G. N. M. ; Jackson, M. F. ; Choy, W. - Y. ; MacDonald, J. F. ; Martins, V. R. ; Prado, V. F. ; Prado, M. A. M. The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-Beta Oligomer Toxicity. JOURNAL OF NEUROSCIENCE 2013, 33, 16552-16564.
Bai, Y. ; Luo, Q. ; Zhang, W. ; Miao, L. ; Xu, J. ; Li, H. ; Liu, J. Highly Ordered Protein Nanorings Designed By Accurate Control Of Glutathione S-Transferase Self-Assembly. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2013, 135, 10966-10969.
Zheng, P. ; Takayama, S. -ichiJ. ; A. Mauk, G. ; Li, H. Single Molecule Force Spectroscopy Reveals That Iron Is Released From The Active Site Of Rubredoxin By A Stochastic Mechanism. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2013, 135, 7992-8000.
Panwar, P. ; Du, X. ; Sharma, V. ; Lamour, G. ; Castro, M. ; Li, H. ; Broemme, D. Effects Of Cysteine Proteases On The Structural And Mechanical Properties Of Collagen Fibers. JOURNAL OF BIOLOGICAL CHEMISTRY 2013, 288, 5940-5950.

2012

Peng, Q. ; Kong, N. ; Wang, H. - C. Eileen; Li, H. Designing Redox Potential-Controlled Protein Switches Based On Mutually Exclusive Proteins. PROTEIN SCIENCE 2012, 21, 1222-1230.
He, C. ; Genchev, G. Z. ; Lu, H. ; Li, H. Mechanically Untying A Protein Slipknot: Multiple Pathways Revealed By Force Spectroscopy And Steered Molecular Dynamics Simulations. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2012, 134, 10428-10435.
Zheng, P. ; Takayama, S. -ichiJ. ; A. Mauk, G. ; Li, H. Hydrogen Bond Strength Modulates The Mechanical Strength Of Ferric-Thiolate Bonds In Rubredoxin. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2012, 134, 4124-4131.
Li, Y. Devin; Lamour, G. ; Gsponer, J. ; Zheng, P. ; Li, H. The Molecular Mechanism Underlying Mechanical Anisotropy Of The Protein Gb1. BIOPHYSICAL JOURNAL 2012, 103, 2361-2368.

2011

Peng, Q. ; Fang, J. ; Wang, M. ; Li, H. Kinetic Partitioning Mechanism Governs The Folding Of The Third Fniii Domain Of Tenascin-C: Evidence At The Single-Molecule Level. JOURNAL OF MOLECULAR BIOLOGY 2011, 412, 698-709.
Zheng, P. ; Li, H. Highly Covalent Ferric-Thiolate Bonds Exhibit Surprisingly Low Mechanical Stability. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2011, 133, 6791-6798.
Cao, Y. ; Li, Y. Devin; Li, H. Enhancing The Mechanical Stability Of Proteins Through A Cocktail Approach. BIOPHYSICAL JOURNAL 2011, 100, 1794-1799.
Zheng, P. ; Cao, Y. ; Bu, T. ; Straus, S. K. ; Li, H. Single Molecule Force Spectroscopy Reveals That Electrostatic Interactions Affect The Mechanical Stability Of Proteins. BIOPHYSICAL JOURNAL 2011, 100, 1534-1541.
Aioanei, D. ; Lv, S. ; Tessari, I. ; Rampioni, A. ; Bubacco, L. ; Li, H. ; Samori, B. ; Brucale, M. Single-Molecule-Level Evidence For The Osmophobic Effect. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2011, 50, 4394-4397.

2010

Li, H. ; Cao, Y. Protein Mechanics: From Single Molecules To Functional Biomaterials. ACCOUNTS OF CHEMICAL RESEARCH 2010, 43, 1331-1341.
Jollymore, A. ; Li, H. Measuring ``unmeasurable'' Folding Kinetics Of Proteins By Single-Molecule Force Spectroscopy. JOURNAL OF MOLECULAR BIOLOGY 2010, 402, 610-617.
Liu, N. ; Peng, B. ; Lin, Y. ; Su, Z. ; Niu, Z. ; Wang, Q. ; Zhang, W. ; Li, H. ; Shen, J. Pulling Genetic Rna Out Of Tobacco Mosaic Virus Using Single-Molecule Force Spectroscopy. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2010, 132, 11036-11038.
Liu, N. ; Bu, T. ; Song, Y. ; Zhang, W. ; Li, J. ; Zhang, W. ; Shen, J. ; Li, H. The Nature Of The Force-Induced Conformation Transition Of Dsdna Studied By Using Single Molecule Force Spectroscopy. LANGMUIR 2010, 26, 9491-9496.
Lv, S. ; Dudek, D. M. ; Cao, Y. ; Balamurali, M. M. ; Gosline, J. ; Li, H. Designed Biomaterials To Mimic The Mechanical Properties Of Muscles. Nature (London, United Kingdom) 2010, 465, 69 - 73.
Zhuang, S. ; Linhananta, A. ; Li, H. Phenotypic Effects Of Ehlers-Danlos Syndrome-Associated Mutation On The Fniii Domain Of Tenascin-X. Protein Science 2010, 19, 2231 - 2239.

2009

Zhuang, S. L. ; Peng, Q. ; Cao, Y. ; Li, H. B. Modulating The Mechanical Stability Of Extracellular Matrix Protein Tenascin-C In A Controlled And Reversible Fashion. Journal of Molecular Biology 2009, 390, 820-829.
Jollymore, A. ; Lethias, C. ; Peng, Q. ; Cao, Y. ; Li, H. B. Nanomechanical Properties Of Tenascin-X Revealed By Single-Molecule Force Spectroscopy. Journal of Molecular Biology 2009, 385, 1277-1286.
Peng, Q. ; Li, H. Direct Observation Of Tug-Of-War During The Folding Of A Mutually Exclusive Protein. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2009, 131, 13347-13354.
Cao, Y. ; Er, K. Shih; Parhar, R. ; Li, H. A Force-Spectroscopy-Based Single-Molecule Metal-Binding Assay. CHEMPHYSCHEM 2009, 10, 1450-1454.

2008

Balamurali, M. M. ; Sharma, D. ; Chang, A. ; Khor, D. ; Chu, R. ; Li, H. B. Recombination Of Protein Fragments: A Promising Approach Toward Engineering Proteins With Novel Nanomechanical Properties. Protein Science 2008, 17, 1815-1826.
Sharma, D. ; Feng, G. ; Khor, D. ; Genchev, G. Z. ; Lu, H. ; Li, H. B. Stabilization Provided By Neighboring Strands Is Critical For The Mechanical Stability Of Proteins. Biophysical Journal 2008, 95, 3935-3942.
Cao, Y. ; Yoo, T. ; Zhuang, S. L. ; Li, H. B. Protein-Protein Interaction Regulates Proteins’ Mechanical Stability. Journal of Molecular Biology 2008, 378, 1132-1141.
Li, H. B. ; Wang, H. C. ; Cao, Y. ; Sharma, D. ; Wang, M. Configurational Entropy Modulates The Mechanical Stability Of Protein Gb1. Journal of Molecular Biology 2008, 379, 871-880.
Cao, Y. ; Kuske, R. ; Li, H. B. Direct Observation Of Markovian Behavior Of The Mechanical Unfolding Of Individual Proteins. Biophysical Journal 2008, 95, 782-788.
Cao, Y. ; Li, H. How Do Chemical Denaturants Affect The Mechanical Folding And Unfolding Of Proteins?. Journal of Molecular Biology 2008, 375, 316-324.
Peng, Q. ; Li, H. B. Atomic Force Microscopy Reveals Parallel Mechanical Unfolding Pathways Of T4 Lysozyme: Evidence For A Kinetic Partitioning Mechanism. Proceedings of the National Academy of Sciences of the United States of America 2008, 105, 1885-1890.
Cao, Y. ; Yoo, T. ; Li, H. B. Single Molecule Force Spectroscopy Reveals Engineered Metal Chelation Is A General Approach To Enhance Mechanical Stability Of Proteins. Proceedings of the National Academy of Sciences of the United States of America 2008, 105, 11152-11157.
Cao, Y. ; Li, H. B. Engineering Tandem Modular Protein Based Reversible Hydrogels. Chemical Communications 2008, 4144-4146.

2007

Cao, Y. ; Balamurali, M. M. ; Sharma, D. ; Li, H. B. A Functional Single-Molecule Binding Assay Via Force Spectroscopy. Proceedings of the National Academy of Sciences of the United States of America 2007, 104, 15677-15681.
Sharma, D. ; Perisic, O. ; Peng, Q. ; Cao, Y. ; Lam, C. ; Lu, H. ; Li, H. B. Single-Molecule Force Spectroscopy Reveals A Mechanically Stable Protein Fold And The Rational Tuning Of Its Mechanical Stability. Proceedings of the National Academy of Sciences of the United States of America 2007, 104, 9278-9283.
Cao, Y. ; Li, H. B. Polyprotein Of Gb1 Is An Ideal Artificial Elastomeric Protein. Nature Materials 2007, 6, 109-114.

2006

Walther, K. A. ; Brujic, J. ; Li, H. B. ; Fernandez, J. M. Sub-Angstrom Conformational Changes Of A Single Molecule Captured By Afm Variance Analysis. Biophysical Journal 2006, 90, 3806-3812.
Sharma, D. ; Cao, Y. ; Li, H. B. Engineering Proteins With Novel Mechanical Properties By Recombination Of Protein Fragments. Angewandte Chemie-International Edition 2006, 45, 5633-5638.
Cao, Y. ; Lam, C. ; Wang, M. J. ; Li, H. B. Nonmechanical Protein Can Have Significant Mechanical Stability. Angewandte Chemie-International Edition 2006, 45, 642-645.

2004

Fernandez, J. M. ; Li, H. B. ; Brujic, J. Response To Comment On "force-Clamp Spectroscopy Monitors The Folding Trajectory Of A Single Protein". Science 2004, 306, 411C-+.