Physical Materials and Materials Biology

Inorganic nanomaterials are of a similar dimension to biological macromolecules and assemblies, and often have unique size-, shape- and material-dependent properties. As a result, these nanomaterials hold great promise for biomedical sciences, with applications as potential therapeutics or sensors which can probe the heterogeneous and complex environment of the cellular interior. Our lab is uniquely positioned to study nanoparticle-biomolecule and nanoparticle-cell interations from the single-molecule and single-particle level. This research also extends to investigating how to controllably interface nanomaterials with biological matter and the development and characterization of new functional photoluminescent and plasmonic nano-probes for use in biological settings.

Protein Corona Formation

Using nanoparticles and nanostructures as chemical and biological probes has been hampered by the fact that proteins in biological fluid inevitably interact non-specifically with the nanomaterial to form a "protein corona" which in turn imparts new biological identity to the probe. We are applying single-molecule and single-particle techniques to study protein corona formation and developing nanoparticle coatings which are resistant to the hard protein corona.

Links:
https://doi.org/10.1021/ja511297d

Breaking the Plasma Membrane Barrier

The plasma membrane poses a barrier to entry of exogenous material. Viral particles have evolved sophisticated mechanisms to circumvent this barrier, but for engineered materials, like functional nanostructures, it still poses a significant obstacle to their deployment. Using our single-particle tracking and multi-resolution microscopy, we are studying the interaction of nanoparticles with the cell membrane, and implementing methods such as "mechanodelivery" to enable exogenous materials to enter the cytoplasm.

Links:
http://dx.doi.org/10.1039/C3NR06468A
http://dx.doi.org/10.1038/nnano.2014.12

Plasmonic Antennas and Actuators

Plasmonic nanoparticles modify their nanoscale environment by converting incident light into intense local electromagentic fields or heat. While the intense local field can modulate the photophysics of nearby molecules and lead to fluorescence enhancement, the generation of nanoscale thermal gradients has interesting implications for particle motion and photothermal therapy. We are using quantitative bulk and single-particle spectroscopy to study these phenomena, as well as developing methods to reproducibly synthesize complex functional plasmonic nanostructures and interface them with biological materials for use as optical antennas or actuators in the cellular space.

Links:
https://doi.org/10.1021/acs.analchem.1c01210

Valency-Defined Nano-Synthons

Thinking of nanoparticles tagged with a defined number of DNA molecules as ‘nano-synthons’ continues to inspire new pathways for developing novel materials and nanotechnologies. Yet, practical limitations have prevented the community from effectively translating this powerful idea to real-world applications: available nano-synthons are confined to small nanoparticles (typically sizes < 40 nm), and they can only be produced in analytical amounts (sufficient only for single-particle proof-of-principle demonstrations). We have put forward a new concept capitalizing on the digital nature of DNA hybridization to enable reagent-scale purification of valency-defined nanoparticles of various sizes, shapes, and materials.

Links:
https://doi.org/10.1021/jacs.2c04744