COMMONS/ Physical Chemistry seminar: Sabrina Leslie

A COMMONS/ Physical Chemistry seminar by Associate Professor Sabrina Leslie, University of British Columbia, Canada

When: 28 September, 14:15-15:00

Where: Lecturehall KC:B

Title: Following the Arrow of Time: Quantitative Particle-to-Cell Biology of Lipid Nanoparticles

Abstract: Lipid nanoparticles (LNPs) are heterogeneous in size, mass, structure, composition, and mRNA loading, yet how this microscopic heterogeneity determines their interactions and fate in biological environments remains poorly understood (Kamanzi et al., ACS Nano, 2026; Graves et al, Analytical Chemistry, 2026). Addressing this problem requires measurements that connect individual nanoparticles in solution to their dynamics across increasing levels of biological complexity.

Here, we use CLiC (Convex Lens-induced Confinement) microscopy together with label-free interferometric scattering (iSCAT), multichannel fluorescence, and cryo-electron microscopy to quantitatively characterize LNPs across the same suite of formulations. We measure the single-particle distributions of particle size, mass, mRNA payload, structure, interaction kinetics, and multi-step dynamics in living cells, allowing us to investigate how formulation-dependent heterogeneity propagates into biological behavior (Boateng, Olsen et al., Nano Letters, 2025; and work in review, 2026).

More broadly, we ask whether “following the arrow of time” of individual nanoparticles—from their initial physical properties through molecular interactions and cellular fate—can reveal quantitative relationships between nanoscale structure and biological function. Such particle-to-cell measurements may help reconcile differences between in vitro characterization and in vivo behavior and provide a more mechanistic basis for understanding and engineering nanomedicines.

“Eyes on All Steps.” (A–C) Particle formulation provides a common axis for our nanoparticle investigations, in collaboration with the Pieter Cullis nanomedicine laboratory at UBC. (D-E) Using quantitative in-solution optical imaging, we investigate biophysical relationships between heterogeneous single-particle properties and single-cell dynamics under out-of-equilibrium conditions, and connect these measurements with in vivo data. Our goal is to uncover how and why nanoparticle properties propagate across biological scales and enable discoveries at the interface of physics, biology, and medicine.