Boron nitride nanosheet is a novel two-dimensional nanomaterial with great potential in biomedical applications. While in biological cells, lipid membranes act as a protective barrier and a gateway regulating transport of substances and signal across the intracellular space. Fundamental understanding how boron nitride nanosheets interact with lipid membranes is a key issue for clarifying the potential risks of these nanomaterials and providing guidance on design of safe biomedical applications.

In this thesis, the interactions between boron nitride nanosheet and phospholipid membranes is investigated with theoretical and experimental approaches, mainly molecular dynamics simulations. Lipid membranes are represented by some simplified and more precise models as the cell membranes contain various components.

We first report that boron nitride nanosheet could extract phospholipids from six types of single component lipid bilayer and affect the ordering of lipid molecules. More specifically, a phase transition is induced by boron nitride nanosheet in the 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer. The structural changes in lipid membranes significantly increase the bending moduli of the membrane and decrease the diffusivity of lipid molecules.

We also show experimentally and theoretically that boron nitride nanosheet disrupts the inner and outer cell membranes of Escherichia coli. The lipid extraction was further confirmed by free energy calculations. A liquid to gel phase transition is induced by boron nitride nanosheet in the outer model membrane of Escherichia coli, indicating boron nitride nanosheet carries higher toxicity to the outer model membrane than to the inner model membrane.

Last but not least, we report that boron nitride nanosheet disrupts the liquid disordered lipid bilayers much more easily compared to the liquid ordered phases. Potential of mean force profiles calculated from umbrella sampling further explain this adsorption preference. When the boron nitride nanosheet is placed at the boundary of the liquid ordered and liquid disordered nanodomains, the liquid ordered domains become much easier to be disrupted due to the present of adjacent liquid disordered domain. The hydrophobic energy of transfer of a lipid molecule from the bilayer to the water is proved as an important determinant for the cytotoxicity of cellular membranes.

These findings may provide new insights into the cytotoxicity of boron nitride nanosheet interacts with cellular membranes, and could be further taken into account for the development of nanocarrier and antibiotics.