Single-molecule Mechanostructural Fingerprinting of Nucleic Acid Conformations

Shrestha P*, Bergal HT, Shih WM, and Wong WP*.
Nucleic Acids Research, Volume 54, Issue 1, 13 January 2026, Link
bioRxiv 2025.05.08.652980; Link
Before Joining UK
Mapping Single-Molecule Protein Complexes in 3D with DNA Nanoswitch Calipers.
Shrestha P, Yang D, Ward A, Shih WM, and Wong WP*.
J. Am. Chem. Soc., 2023 December 14, 145 (51), 27916-27921.Link
Single-molecule mechanical fingerprinting with DNA nanoswitch calipers.

Shrestha P, Yang D, Tomov TE, MacDonald JI, Ward A, Bergal HT, Krieg E, Cabi S, Luo Y, Nathwani B, Johnson-Buck A, Shih WM*, Wong WP*.
Nat Nanotechnol. 2021 Dec;16(12):1362-1370. Link
Featured as research highlights,
- DNA Nanoswitch Calipers Created as Possibly World’s Tiniest Ruler For Fingerprinting Proteins, Genetic Engineering and Biotechnology News, October 22, 2021. genengnews
- Tiny Ruler takes measure of single protein molecules, Chemistry World, November 2, 2021. tiniest-ruler
Decreased water activity in nanoconfinement contributes to the folding of G-quadruplex and i-motif structures.
Jonchhe S, Pandey S, Emura T, Hidaka K, Hossain MA, Shrestha P, Sugiyama H, Endo M, Mao H.
Proc Natl Acad Sci USA. 2018 Sep 18;115(38):9539-9544. Link
A new concentration jump strategy reveals the lifetime of i-motif at physiological pH without force.
Jonchhe S, Shrestha P, Ascencio K, Mao H.
Anal Chem. 2018 Mar 6;90(5):3205-3210. Link
Single-Molecule mechanochemical pH sensing revealing the proximity effect of hydroniums generated by an alkaline phosphatase.
Shrestha P, Cui Y, Wei J, Jonchhe S, Mao H.
Anal Chem. 2018 Feb 6;90(3):1718-1724. Link
Confined space facilitates G-quadruplex formation.
Shrestha P, Jonchhe S, Emura T, Hidaka K, Endo M, Sugiyama H, Mao H.
Nat Nanotechnol. 2017 Jul;12(6):582-588. Link
Featured as research highlights,
- Chemists create microscopic environment to study cancer cell growth, Science Daily, 2017.
- Nanocages dramatically facilitate structure formation of biomolecules, Eurekalert, 2017.
Mechanochemical sensing of single and few Hg(II) ions using polyvalent principles.
Mandal S, Selvam S, Shrestha P, Mao H.
Anal Chem. 2016 Oct 4;88(19):9479-9485. Link
Mechanical properties of DNA origami nanoassemblies are determined by Holliday junction mechanophores.
Shrestha P, Emura T, Koirala D, Cui Y, Hidaka K, Maximuck WJ, Endo M, Sugiyama H, Mao H.
Nucleic Acids Res. 2016 Aug 19;44(14):6574-82. Link
Mechanochemical Sensing: A Biomimetic Sensing Strategy
Shrestha P, Mandal S, and Mao H.
ChemPhysChem 2015, 16(9):1829-37. Link
Interaction of G-quadruplexes in the full-length 3' human telomeric overhang.
Abraham Punnoose J, Cui Y, Koirala D, Yangyuoru PM, Ghimire C, Shrestha P, Mao H.
J Am Chem Soc. 2014 Dec 31;136(52):18062-9. Link
Single-molecule mechanochemical sensing using DNA origami nanostructures.
Koirala D, Shrestha P, Emura T, Hidaka K, Mandal S, Endo M, Sugiyama H, Mao H.
Angew Chem Int Ed Engl. 2014 Jul 28;53(31):8137-41. Link
- Featured in the Journal’s cover story.
Nascent RNA transcripts facilitate the formation of G-quadruplexes.
Shrestha P, Xiao S, Dhakal S, Tan Z, Mao H.
Nucleic Acids Res. 2014 Jun;42(11):7236-46. Link
Yoctoliter thermometry for single-molecule investigations: a generic bead-on-a-tip temperature-control module.
Koirala D, Punnoose JA, Shrestha P, Mao H.
Angew Chem Int Ed Engl. 2014 Mar 24;53(13):3470-4. Link
- Featured in the Journal’s cover story.
- Featured as a research highlight,
“A controlled jump”. Moscatelli, A. Nature Nanotech 9, 245 (2014).
Book chapters
Mechanochemical Sensing: A Book chapter
Shrestha P, Mandal S, and Mao H.
RNA and DNA Diagnostics (eds. Erdmann, V.A., Jurga, S. & Barciszewski, J.) 2015, 241-258 (Springer International Publishing). Link