Nanoparticle behaviour at the cell membrane

NPs are materials with size scales on the order of molecules. The same small sizes that impart such unique and exotic properties also make them potential cell invaders. Models based on realistic data are required to predict the toxicity of new NPs with minimal animal testing early in the design phase.

The scope is huge in terms of potential NPs, physicochemical properties, cell types and other factors. Scientists launched the EU-funded imitative MEMBRANENANOPART to develop models of NP interactions with the cell membrane, entry into cells and subsequent toxicity. The first half of the project has focused on NP-biomolecule and NP-cell membrane interactions.

Project models are providing a description of the protein adsorption layer (protein corona) that forms on the surface of NPs upon their entrance into biological media and plays a role in their interaction with living matter. Work on atomistic molecular dynamics led to optimisation of atomistic force fields for modelling hard-soft interfaces such as contact regions between solid inorganic NPs and biomolecules.

With a generic coarse-grained model of a protein globule, the team studied adsorption of the most common plasma proteins on generic NP surfaces. Scientists modelled aggregation of the five most common engineered NP groups to gain insight.

Models are also describing how the NP crosses the cell membrane. The team studied translocation of titanium oxide NPs through lipid monolayers and bilayers and began formulation of methodologies based on outcomes.

Assessment of the toxicological impact of the NPs will provide the basis for subsequent correlation with properties such as NP size, shape, surface charge, and hydrophobicity or hydrophilicity. Scientists developed a systematic methodology for quantitative assessment of toxicity enabling comparison of data from different sources.

MEMBRANENANOPART outcomes will provide predictive tools for NP designers linking NP physicochemical properties with cell toxicity. The robust screening approach with minimal use of in vivo testing will ensure design of nanomaterials that are safe for humans and the environment.