Rebecca Pinals, University of California-Berkeley
"Elucidating Protein Corona Formation on Nanoparticles in Biological Environments"
Engineered nanoparticles are increasingly used for biological sensing, imaging, and delivery due to their distinctive optical and physical properties. Specifically, DNA function- alized single-walled carbon nanotube (DNA-SWCNT) probes operate at spatiotemporal scales necessary to capture information on chemical signaling, such as neuromodulation in the brain.1 The critical – and often overlooked – challenge with these nanoscale tools is understanding the fundamental mechanisms of interaction between the nanoprobe and
the system they are designed to query. When a nanoparticle enters a biological system, the surface becomes rapidly coated with proteins to form the “protein corona”. Binding of proteins to the nanoparticle disrupts intended nanoparticle functionality and leads to unpredictable in vivo outcomes.
An incomplete understanding of the protein corona remains a paramount barrier to successfully implementing nanotechnologies within biological environments. Herein, I present multimodal char- acterization of (i) protein corona composition, (ii) driving forces of formation, and (iii) kinetics of protein adsorption on DNA-SWCNTs in relevant biological media. I have optimized a platform to quantitatively characterize protein corona composition formed on nanoparticles by mass spectrometry-based proteomics and de- termined abundant and differentially enriched vs. depleted corona proteins. By varying incubation conditions of DNA-SWCNTs in biofluids, I investigated the role of electrostatic and entropic interactions driving selective protein corona formation. To study the dynamic exchange of biomolecules on the SWCNT surface, I developed a multiplexed fluorescence assay that enables real-time tracking of biomolecule adsorption and desorption events.3 This corona exchange assay is generic towards the study of vari- ous biomolecules on nanoparticles, and enables study in solution rather than on a surface-immobilized, less biologically relevant, setting.
Understanding the protein corona composition, driving forces of formation, and dynamics under relevant solution conditions informs design and synthesis of nanotechnology-based tools applied in protein-rich environments. Although corona formation can impair nanobiotechnology efficacy, it also presents an opportunity to create improved protein-nanoparticle architectures by exploiting selective protein adsorption to the nanoparticle surface In this work, I developed techniques and analyses to characterize the in situ protein corona and employ this knowledge towards rational design of nanobiotechnologies.
Rebecca is an NSF Graduate Research Fellow and PhD candidate in the UC Berkeley Department of Chemical and Biomolecular Engineering. She received her BS in chemical engineering with honors from Brown University in 2016, where her research focused on heterogeneous catalysis for biofuel production. Rebecca’s current research at UC Berkeley with Prof. Markita Landry focuses on engineering nanomaterials to probe biological systems. Her work has elucidated the mechanisms and effects of biomolecule adsorption on nanomaterial surfaces, and has applied this knowledge to develop robust nanobiotechnologies with more seamless translation to in vivo applications. She has authored 12 peer-reviewed publications, manages two research grants, and is a co-inventor on two provisional patents. For her research accomplishments, Rebecca has received numerous awards, including the CAS Future Leader Award and the ACS Women Chemists Committee/Merck Research Award, and is a Schmidt Foundation campus finalist and an MIT Rising Star in Chemical Engineering. She has additionally received 1st place in the Bionanotechnology Graduate Student Award Session and 2nd place in the Student Competition in Bio-Sensors for her talks at the 2020 AIChE annual meeting. Beyond research, Rebecca is passionate about mentoring students in research and teaching college and graduate level courses. For her teaching, Rebecca has received the Excellence in Teaching Award and the Outstanding Graduate Student Instructor Award, granted to the top instructors on the UC Berkeley campus. She also leads local science outreach programs that encourage participation in STEM, including Expanding Your Horizons and Bay Area Scientists in Schools.