Research

Our research focuses on developing and applying state-of-the-art single-molecule methods to characterize and understand the properties of nanoscale materials and biological systems. Compared with traditional ensemble measurements, the single molecule approach removes ensemble averaging, so that distributions and fluctuations of molecular properties can be characterized and transient intermediates identified. The single-molecule techqniues we employ include single-molecule fluorescence imaging, single-molecule FRET, single-molecule tracking, super resolution localization microscopy, and magnetic tweezers. Our research program provides students with scientific training spanning from sophisticated microscopy/spectroscopy techniques, rigorous data analyses to protein and genetic engineering using modern molecular biology techniques, as well as nanotechnology and nanomaterials. Currently our research has the following directions (each with a few exemplary publications).

(1) Single-molecule catalysis.

This research direction in our group is to develop and apply single-molecule methods to study the catalytic, photocatalytic, electrocatalytic, and photoelectrocatalytic properties of nanoscale materials and small molecule catalysts. Currently, we are working on:

• Single-nanoparticle catalysis
  • Single-nanoparticle catalytic dynamics; e.g., Nature Mater. 2008, JACS 2010, Nano Lett. 2012.
  • Spatial reactivity pattern within single nanocatalysts; e.g., Nature Nanotech. 2012, JACS 2013.
  • Bimetallic enhancement at metal-metal interfaces in single nanocatalysts; e.g., ACS Cent. Sci. 2017.
  • Catalysis communication and cooperativity in single nanocatalysts; e.g., Nature Chem. 2018.
  • Nanoscale cooperative adsorption of molecules on single nanocatalysts; e.g., Nature Commun. 2021.
• Electrocatalysis
  • Single carbon nanotube electrocatalysis; e.g., Nano Lett. 2009.
• Photoelectrocatalysis
  • Optimizing catalyst modification of photoanodes for solar water splitting; e.g., Nature 2016.
  • Benchmarking photocurrent loss from single particle-particle interfaces; e.g., Nano Lett. 2019.
  • Rational optimization of photocatalyst morphology for micropollutant decontamination; e.g., Nature Chem. 2019.
  • 2D inter-facet junction effects on 3D particulate photoelectrodes; e.g., Nature Mater. 2022.
• Plasmonic catalysis
  • Catalytic hotspots at nano-gaps of plasmonic nanostructures; e.g., ACS Nano 2018.
• Polymerization catalysis
  • Single-polymer growth dynamics during living polymerization; e.g., Science 2017, ACS Cent. Sci. 2022.
  • Conjugated polymers: single-chain polymerization kinetics and conformational mechanics; e.g., Chem 2021.
  • Optical sequencing of single synthetic polymers; e.g., Nature Chem 2024.

(2) Single-molecule bioinorganic/biophysical chemistry.

Here we develop and apply single-molecule methods to understand how metalloproteins function both in vitro and in living cells (i.e., bioinorganic chemistry) as well as how protein folding occurs in living cells (i.e., biophysical chemistry). Our current efforts focus on:

• Transcription regulation by metalloregulators
  • Engineered DNA Holliday junctions as single-molecule reporters of protein-DNA interactions; e.g., JACS 2007.
  • Mechanistic pathways for transcription regulation; e.g., PNAS 2012, PNAS 2015.
  • Transcription regulation mechanism in living cells; e.g., Nature Commun. 2015, Nucleic Acids Res. 2020, PNAS 2020.
• Metal trafficking by metallochaperones
  • Nanovesicle trapping for studying weak protein interactions at the single-molecule level; e.g., JACS 2008.
  • Dynamic protein interactions for versatile metal trafficking; e.g., JACS 2012.
• Metal efflux via muticomponent efflux pumps
  • Adaptor protein mediated metal-sensing assembly of efflux pumps; e.g., PNAS 2017.
  • Molecular mechanobiology of bacteria: mechanical stress induced discruption of metal efflux complex in cells; e.g., PNAS 2019.
• Dynamics of molecular chaperones in cells
• Trigger factor – the first chaperone that interacts with the nascent peptide at the ribosome; e.g., Mol. Microbiol. 2016.
• Electron and energy transport pathways in inorganic-microbe hybrids
• Energy conversion pathways in semiconductor/Ralstonia hybrids for bioplastic production; e.g., Nature Chem. 2023.

(3) Method development.

In pursuit of our scientific interests, we also develop new methods or extend/improve existing methods to enable new experiments:

• CREATS: Coupled-REaction Approach Toward Super-resolution imaging; Nature Chem 2024.
• Single-cell multimodal imaging for uncovering energy conversion pathways in biohybrids; e.g., Nature Chem. 2023.
• Multimodal sub-to-single particle functional imaging of photoelectrochemistry; e.g., Nature Mater. 2022.
• COMPEITS: an optical technique for super-resolution imaging of nonfluorescent reactions; e.g., Nature Chem. 2019.
• Magnetic tweezers approach to study real-time single-molecule polymerization; e.g., Science 2017.
• Sub-particle photoelectrochemical current mapping; e.g., Nature 2016.
• Site-selective catalyst deposition on single particles; e.g., Nature 2016.
• SMT+SCQPC: Single-Molecule Tracking coupled with Single-Cell Quantitation of Protein Concentration; e.g., Nature Commun. 2015.
• ITCDD: Inverse Transformation of Confined Displacement Distribution; e.g., JPC-B 2015.
• Nanovesicle trapping to enable smFRET study of weak protein interactions; e.g., JACS 2008.
• Engineered DNA Holliday junctions as general smFRET reporters for protein-DNA interactions; e.g., JACS 2007.