Research Overview
Research Overview
We are fascinated by nanoparticles assembled from biomolecular building blocks. Since these nanoparticles are made of molecules like proteins or lipids, they are self-assembled by many weak noncovalent interactions, but they ultimately form singular objects. This leads us to ask many questions about their assembly and molecular behavior, such as:
How do molecular contacts and chemical environment influence physical properties like cargo loading and density?
Conversely, how does the physical assembly affect access to internalized cargo such as enzymes?
What principles do biological nanocontainers use that we could apply for drug delivery or for generating specific molecules?
How can we measure these effects on a benchtop microscope?
A key piece in studying these objects is that they are highly heterogeneous in their properties: each object is different in terms of aspects like their size, stoichiometry, and molecular arrangement within the particle, which means that we need to observe multiple properties simultaneously on single objects.
In this ensemble of capsids, there are two populations of 1) small blue particles and 2) large yellow particles. As well, the dynamics of each object (for example their instantaneous motion) are random and unique. The ensemble average of this system is a mid-sized green particle with little motion. By contrast, single-particle experiments are designed to measure the unique characteristics of each object.
We will be developing and harnessing sensitive single-particle observation techniques such as anti-Brownian trapping, single-molecule spectroscopy, and cryo-electron microscopy to determine relationships between the various properties in these soft nanoparticle systems. These methods will allow us to observe single objects with unprecedented detail and inspire new strategies for designing next-generation biomolecular nanoparticles.