Physical mechanisms of nanoparticle-membrane interactions: A coarse-grained study
Massimiliano Paesani1,2,3, Ioana M Ilie1,2,3
1Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, The Netherlands.
The Journal of Chemical Physics
|February 25, 2026
Summary
Flexible nanoparticles show promise for drug delivery but face cellular barriers. Simulations reveal how nanoparticle properties influence membrane interactions and cellular uptake, guiding the design of more effective nanocarriers.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Computational Biophysics
Background:
- Nanoparticles are crucial for targeted therapies, diagnostics, and vaccines.
- Clinical translation is hindered by biological barriers affecting cellular uptake and efficacy.
- Nanoparticle-membrane interactions dictate adhesion, wrapping, and engulfment, controlling internalization.
Purpose of the Study:
- Investigate physical mechanisms of cellular uptake for semi-flexible nanocarriers.
- Understand how nanoparticle properties influence interaction with lipid bilayers.
- Provide design principles for optimizing nanoparticle cellular internalization.
Main Methods:
- Coarse-grained simulations of semi-flexible nanocarriers interacting with a lipid bilayer.
- Utilized metaparticle model for flexible nanoparticles and Cooke-Deserno model for membranes.
- Systematically varied nanoparticle adhesion strength and topology.
Main Results:
- Identified distinct interaction regimes: surface adhesion, trapping, wrapping, and endocytosis.
- Correlated interaction regimes with nanoparticle shape, size, and surface properties.
- Established quantitative design principles for enhancing cellular uptake.
Conclusions:
- Nanoparticle deformability can enhance cellular entry probability.
- Interplay between nanoparticle properties and membrane interactions governs internalization.
- Framework offers predictive insights for designing next-generation soft nanocarriers.
