The increasing applications of nanotechnology in medicine rely on the fact that engineered nanomaterials, such as diagnostic and therapeutic nanoparticles, are able to translocate across the cellular membrane and reach their site of action without toxic effects. One of the first steps into assessing the NP cytotoxicity requires a thorough understanding of the nanoparticle-membrane interaction mechanism, which can be addressed with computer simulations. We use computational approaches for the construction of functionalized magnetite MNPs of different shape, size, and surface chemistry. Initially, a generic code that builds the model of a magnetite NP core is developed. The growing planes of the crystal, which are relative to the minimum surface energies, are used to extend the size and shape of the NP. This approach is generalized by developing an algorithm that constructs different crystal morphologies for a given crystal based on its preferred growing planes, the Miller indices and a user-defined size of the crystal. Subsequently, another algorithm is developed to attach ligands on the MNP core. We have applied these tools for the construction of magnetite nanoparticles coated with polyvinyl alcohol or polyarabic acid and performed Molecular Dynamics (MD) simulations to investigate the MNP in contact with a model cell membrane. In another approach, we use coarse-grained MD to investigate the partitioning of an anionic, ligand-decorated NP in model membranes containing cholesterol. Simulations reveal that the hydrophobic and hydrophilic ligands of the NP surface rearrange to form optimal contacts with the lipid bilayer, leading to the so-called snorkeling effect. Inside cholesterol-containing bilayers, the NP induces rearrangement of the structure of the lipid bilayer in its vicinity from the liquid-ordered to the liquid phase spanning a distance almost twice its core radius. When several anionic, ligand-coated NPs are embedded in the model membrane, NPs tend to form linear clusters, or chains. Analysis of the driving forces for this association reveals an important role of the recently discovered orderphobic effect. Verification of our findings followed with SEM experiments.

Studying nanoparticle-membrane interactions using MD simulations

255th National Meeting (2018)

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