Speaker
Description
Computational Modelling of Protein Corona Formation on Lipid Nanoparticles: Hard Corona and Polydispersity Effects
Fiona Gallach1,2*, Oriol Vilanova1,2, Alberto Martinez-Serra3, Marco Monopoli4, Giancarlo Franzese1,2
1Departament de Física de la Matèria Condensada, Facutat de Física, Universitat de Barcelona, Marti i Franques 1, 08028 Barcelona, Spain
2Institute of Nanoscience and Nanotechnology (IN2UB), Universitat de Barcelona, Marti i Franques 1, 08028 Barcelona, Spain
2 Barcelona Supercomputing Center (BSC), Barcelona, Spain
3 Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
fgallach7@alumnes.ub.edu
Introduction
When lipid nanoparticles (LNPs) enter biological fluids, proteins adsorb onto their surface, forming a biomolecular corona that consists of a tightly bound hard corona (HC) and a loosely associated soft corona (SC). This corona influences their pharmacokinetics and cellular fate. Computational modeling of HC formation is essential for the rational design of LNP-based drug delivery systems 1.
Materials & Methods
A coarse-grained (CG) model was employed to describe human serum albumin (HSA)–LNP interactions using a potential that combines van der Waals attraction, electrostatic repulsion, and Born repulsion. The interaction strength was calibrated by fitting simulated adsorption isotherms to experimental surface coverage data (0–10 mg/mL HSA) for an LNP with radius R = 90 nm, yielding an optimal interaction strength of 7.25 kBT. Additional simulations at R = 87 nm and R = 93 nm were performed to mimic the experimental polydispersity [2].
Results and Discussion
The calibrated model closely matches the experimental HSA adsorption isotherm, accurately capturing both initial adsorption and surface saturation. Simulations at R = 87 nm and R = 93 nm align well with the baseline case, suggesting that a polydispersity of ±3 nm has minimal impact on HC formation. Consistently, the potential wells for R = 50 nm, 90 nm, and 93 nm are nearly identical in depth and position, indicating that the binding energy landscape remains largely unaffected by small changes in curvature within this size range. Ongoing analysis, including cooperative effects from three-body protein–protein–NP interactions, aims to further refine the model's alignment with experimental results. These preliminary findings confirm the effectiveness of the CG framework for modeling HSA corona formation and pave the way for future research on Vroman-type competitive exchange under physiological conditions.
References
1 F. Spinozzi, P. Moretti, D. R. Perinelli, G. Corucci, P. Piergiovanni, H. Amenitsch, G. A. Sancini, G. Franzese, and P. Blasi. Small-angle x-ray scattering unveils the internal structure of lipid nanoparticles. Journal of Colloid and Interface Science, 662, 446 (2024).
[2] O. Vilanova, A. Martinez-Serra, M. P. Monopoli, and G. Franzese. Characterizing the hard and soft nanoparticle-protein corona with multilayer adsorption. Frontiers in Nanotechnology, 6, 1531039, (2025).
