Mechano-analytical chemistry: a new interdisciplinary field
By combining Analytical Chemistry and Single-Molecule Biophysics, we created a new chemistry field: Mechano-Analytical Chemistry. We have used the following techniques to develop this new field:
Micro total analysis system (mTAS), a.k.a. lab-on-a-chip, integrates a variety of lab components on a chip as small as one inch square in area. In a typical lab-on-a-chip scheme, chemicals can be synthesized, purified and analyzed on a single chip. The technique is indispensable in the emerging fields such as genomics and proteomics, where huge sets of data are collected and analyzed. It is also very useful in the screening processes to identify promising drug leads or optimal conditions for crystallization. The low cost and high-throughput capability make this technique ideal for sensor development. Combining with laser tweezers or magnetic tweezers (see below), our lab is interested in the methodology development and bioanalytical application of this technique, for example in the fields of ultra sensitive sensors and screening methods.
Since the discovery of the laser tweezers in the 1980s, the application of this technique has been mostly limited to the physics where it originated. The lag of the application in chemistry can be attributed to the following reasons. First, the tiny amount of the material contained inside a trapped object prevents the use of many traditional detection methods, such as UV-vis and IR. Second, to build a strong optical trap, objectives with short working distance are often used. This leaves little accessible room to incorporate other detection methods. Our lab uses unique capabilities of the laser tweezers, i.e., force detection in the range of piconewtons and spatial measurement down to Angstroms, to follow the chemical interactions such as binding events between receptors and ligands.
Compared to laser tweezers (see above), magnetic tweezers have the advantages of lower force range (fN-pN), less drift, and full compatibility with a typical lab-on-a-chip layout. Most importantly, magnetic tweezers have high-throughput. Magnetic objects can be easily incorporated into microfluidic channels on a chip and manipulated by an external magnet. These objects can be used to control the fluidics at the micrometer scale, which is one of the most difficult tasks in the development of lab-on-a-chip techniques.
Using laser- and magnetic-tweezers on a chip, we have been investigating fundamental properties of biomacromolecules including DNA and proteins. In addition, we have pioneered an ultrasensitive and high-throughput biosensing method called Single-Molecule Mechanochemical Sensing (or SMMS). With many patents awarded, we have used SMMS to detect trace levels of biomarkers for various diseases, as well as toxins such as mercury in the environment.
Our research is interdisciplinary. We carry out many collaborative projects with groups from materials and biosciences. Incoming members have ample opportunities to learn subjects through coworkers from other fields.
- "A Mechanosensor Mechanism Controls the G-Quadruplex/i-Motif Molecular Switch in the MYC Promoter NHE III," Caleb Sutherland, Yunxi Cui, Hanbin Mao, Laurence Hurley. Journal of the American Chemical Society, 2016, in press.
- "Mechanical Properties of DNA Origami Nanoassemblies are Determined by Holliday Junction Mechanophores," P. Shrestha, T. Emura, K. Deepak, Y. Cui, H. Kumi, W. J. Maximuck, M. Endo, H. Sugiyama, H. Mao. Nucleic Acids Research, 2016, 44, 6574-6582.
- "A Molecular Tuning Fork in Single-Molecule Mechanochemical Sensing," Shankar Mandal, Deepak Koirala, Sangeetha Selvam, Chiran Ghimire, Hanbin Mao. Angewandte Chemie International Edition, 2015, 54, 7607-11.
- "Interaction of G-Quadruplexes in the Full-Length 3' Human Telomeric Overhang," J. A. Punnoose, Y. Cui, D. Koirala, P. M. Yangyuoru, C. Ghimire, P. Shrestha, H. Mao. JACS, 2014, 136(52), 18062-18069. DOI: 10.1021/ja510079u.
- "Direct Quantification of Loop Interaction and pi-pi Stacking for G-Quadruplex Stability at the Sub-Molecular Level," C. Ghimire, S. Park, K. Iida, P. M. Yangyuoru, H. Otomo, Z. Yu, K. Nagasawa, H. Sugiyama, H. Mao. JACS, 2014, 136, 15537-15544.
- "Quantification of Topological Coupling Between DNA Superhelicity and G-Quadruplex Formation," S. Selvam, D. Koirala, Z. Yu, H. Mao. Journal of the American Chemical Society, 2014, 136, 13967-13970. dx.doi.org/10.1021/ja5064394l.
- "Single Molecule Mechanochemical Sensing Using DNA Origami Nanostructures," D. Koirala, P. Shrestha, T. Emura, K. Hidaka, S. Mandal, M. Endo, H. Sugiyama, H. Mao. Angewandte Chemie International Edition, 2014, 53, 3470-3474.
- "A Generic Bead-on-a-Tip Temperature-Jump Module with Yoctoliter Thermometry for Single-Molecule Investigations," Deepak Koirala, Jibin Abraham Punnoose, Prakash Shrestha, Hanbin Mao. Angewandte Chemie International Edition, 2014, 53, 3470-3474.
- "Long-Loop G-Quadruplexes are Misfolded Population Minorities with Fast Transition Kinetics in Human Telomeric Sequences," D. Koirala, C. Ghimire, C. Bohrer, Y. Sannohe, H. Sugiyama, H. Mao. Journal of the American Chemical Society, 2013, 135, 2235-2241.
- "Click-Chemistry Assisted Single-Molecule Fingerprinting Reveals a 3D Biomolecular Folding Funnel," Zhongbo Yu, Deepak Koirala, Yunxi Cui, Leah F. Easterling, Yuan Zhao, Hanbin Mao. Journal of the American Chemical Society, 2012, 134, 12338-12341.
- "The Tertiary DNA Structure in the Single-Stranded hTERT Promoter Fragment Unfolds and Refolds by Parallel Pathways via Cooperative or Sequential Events", Z. Yu, V. Gaerig, Y. Cui, H. Kang, et.al. JACS, 2012, 134, 5157-5164.
- “A Single-Molecule Platform for Investigation of Interactions between G-quadruplexes and Small-Molecule Ligands”. D. Koirala, S. Dhakal, B. Ashbridge, Y. Sannohe, R. Rodriguez, H. Sugiyama, S. Balasubramanian, H. Mao, Nature Chemistry, 2011, 3, 782-787.
- “Detection of Single Nucleotide Polymorphism Using Tension-Dependent Stochastic Behavior of a Single-Molecule Template”. Deepak Koirala, Zhongbo Yu, Soma Dhakal, Hanbin Mao, Journal of the American Chemical Society, 2011, 133, 9988-91.
- “Coexistence of an ILPR i-motif and a partially folded structure with comparable mechanical stability revealed at the single molecular level”, S. Dhakal, J. Schonhoft, D. Koirala, Z. Yu, S. Basu, H. Mao, JACS, 2010, 132, 8991-8997.
- "ILPR G-quadruplexes Formed in Seconds Demonstrate High Mechanical Stabilities", Z. Yu, J. D. Schonhoft, S. Dhakal, R. Bajracharya, R. Hegde, S. Basu, H. Mao, Journal of the American Chemical Society, 2009, 131,1876–1882.