Effects of Graphene on lipid vesicles: a combination of experiments and simulations

Abstract

Graphene is a carbon-based nanomaterial which has gained popularity in the field of biomedicine and biotechnology because of its exceptional properties. This new interest also unleashed concerns about the possible toxic effects of graphene on living beings. This work is focused on analyzing the interaction between graphene and the plasma membrane of eukaryotic cells. For this purpose, simple in vitro lipid vesicles mimicking cell membranes are produced to perform experiments where the interaction can be observed through an optical microscope. Molecular Dynamics simulations have also been performed to understand the interaction at a molecular level. Two types of artificial vesicles have been produced for different purposes. The first type is composed of a binary mixture of lipids (POPC and cholesterol) and it is used to study the interaction with graphene. The results of both experiments and simulations show an attractive interaction and subsequent insertion of graphene inside the lipid bilayer which indicates that the bilayer makes a good solvent for graphene and, thus, a site of graphene bioaccumulation. The second type is composed of a ternary mixture of lipids (DOPC, DPPC and cholesterol), which leads to vesicles with a segregation of two phases that can be distinguished through fluorescence microscopy. It is well known that cell membranes are not homogeneous, in fact, they are composed of domains: a liquid-ordered phase formed by saturated lipids and cholesterol and a liquid-disordered phase formed by unsaturated lipids. The biological complexity of the domains in the cell membrane can be approached by means of the two-phase vesicles which are used to test if graphene has a preference for a specific phase. MD simulations were also performed to study the insertion process of graphene in each phase. Both the experiments and simulations show that graphene has no preference for any of the phases. Molecular dynamics simulations reveal that the graphene insertion in the liquid-ordered phase takes place in twice the time of the insertion in the liquid-disordered phase