Nanoparticle Clustering within Lipid Membranes Induced by Surrounding Medium. Nanomechanical and Thermotropic Study on Model Lipid Membranes

The research of the nanoparticle (NP) delivery systems and the use of NPs both for diagnostic and therapeutic purposes have created a need for understanding the complex interactions of NPs with cells. Membrane-NP interactions are of crucial importance both for the cell uptake and toxicological investigations. For that reason, lipids that are the cell membrane building blocks, have been used as simplified model systems to study not only the mechanical properties of the membranes and their interactions with different molecular species, but also their structural organization in, for example, marine ecosystems, which are particularly sensitive to the toxicological environmental effects [1]. The interactions between hydrophobic or semihydrophobic gold and silver NPs and a dimyristoylphosphatidylcholine (DMPC) bilayer as a model cell membrane in two ionic solutions result in the structural reorganization within the bilayer manifested as locally increased nanomechanical compaction in the vicinity of NP clusters as well as changed overall thermotropic properties. The reorganization was investigated by AFM imaging, force spectroscopy and IR spectroscopy. The effects of NP surface charge and hydrophobicity were examined by using two different dithiole ligands. First, hydrophobic stearyl amine was coupled to lipoic acid coated gold and silver NPs. Second, newly synthesized positively charged semihydrophobic ligand containing additional amine group was used to functionalize gold and silver NPs by ligand exchange method. The mean diameter of the NPs estimated from the mean heights as observed by AFM imaging was 3 nm, i.e. small enough to enable embedding of NPs within the bilayer. The ligand effect of NPs on a non-local level of the bilayer phase change (bulk property) has been recorded as lowering of the phase transition temperature at the most by 1.0 C in PBS and as increasing of the phase transition temperature at the most by 0.5 C in seawater. The force spectroscopy results, on the other hand, indicated that (semi)hydrophobic NPs increased the bilayer density around NP clusters and thus locally increased lateral compaction of the bilayer. The strengthening effect was observed for both the silver and the gold NPs in a high ionic strength solution such as seawater (SW), while it was absent under physiological conditions. The local lipid rearrangement induces the long range lipid reorganization resulting in the bilayer phase transition shifting towards lower or higher temperatures depending on the solution ionic strength.