ChBE Seminar Series: Quantitative microscopy of nucleation and protein aggregation phenomena
Speaker: Taylor Woehl, ChBE Assistant Professor, UMD
Title: Quantitative microscopy of nucleation and protein aggregation phenomena
In this talk I will discuss advanced optical and electron microscopy methods developed in our lab and their applications for visualizing nanoscale transport and kinetic phenomena, such as nanoparticle nucleation and protein aggregation. In this first part of the talk I will discuss recent work using liquid cell transmission electron microscopy (LC-TEM) to directly visualize nanoparticle nucleation at a solid-liquid interface in real time with nanometer spatial resolution. Using this approach, we demonstrate that heterogeneous nucleation of silver nanocrystals at a macroscopically uniform silicon nitride-water interface occurs in discrete nanoscale pockets on the interface. Careful characterization of the interface with atomic force microscopy and covalent nanoparticle labeling revealed pockets of surface functional groups on the interface act as preferential nucleation sites. These results challenge previously held beliefs about nucleation on uniform interfaces, showing that nanoscale variations in surface chemistry propagate nanoscale variations in nucleation kinetics. In the second part of my talk, I will describe our recent development of interferometric scattering microscopy (IFS) for characterization of sub-micron protein aggregates in biopharmaceuticals. IFS rapidly and simply characterizes elusive nanometer sized protein aggregates that may cause immunogenicity in patients, enabling quantifying particle size distribution, particle counts, and even absolute particle size. IFS could enable rapid QC testing of biopharmaceuticals and enhance the safety of these life-saving drugs. Recent applications using IFS to investigate protein aggregation kinetics under high shear stress and the tertiary structure of protein aggregate surfaces will be shown.