Molecular Insights into the Interactions between Lipid Membranes and Two-Dimensional Nanomaterials

Description

The rapid development of two-dimensional (2D) nanomaterials has triggered promising biomedical applications such as nano-sensing, nano-imaging, and drug delivery. However, the clinical realization of these emerging applications is challenged by the cytotoxicity of nanomaterials. Experimental studies have revealed the complexity of nanotoxicity, which depends on properties of nanomaterials (e.g., size, dosage, surface characteristic, etc.) and surrounding conditions, such as temperature. To thoroughly understand the cytotoxicity of 2D nanomaterials, molecular and thermodynamic insights into the bio-nano interaction between biological systems and 2D nanomaterials are necessary. However, this information is difficult to access using experimental techniques.In the proposed work, molecular dynamics (MD) simulation, which is taken as a computational microscope, will be used to investigate the coupling of 2D nanomaterials and lipid membranes. Lipid membranes are simplified models of the plasma cell membranes, which protect a biological cell from its environment and play key roles in a huge number of cellular activities. The sharp edges of 2D nanomaterials can penetrate cell membranes, which could lead to leakage and ultimate cell death. Nanosheets may also affect cell membrane functions and alter crucial properties in a way that reduces cell viability.The goal of the proposed work is to gain molecular insights into the physical interaction between nanosheets and lipid membranes, potential side effects of nanosheets on lipid membranes, and thermodynamic driving forces that dominate behaviors of nanosheets and lipids. First, we will perform simulations to explore the atomistic interaction morphology of lipid membranes with nanosheets of varying sizes, orientations, and hydrophobicity. Then, we will evaluate the modeled cytotoxicity of different interaction states by analyzing the effects of nanosheets on membrane properties including: membrane integrity, lipid diffusivity, membrane rigidity, and lipid flip-flop rate. Next, the evolution of interaction morphologies will be decomposed, molecular motions and dynamic pathways will be identified. Furthermore, thermodynamics that dominate different molecular motions and dynamic pathways will be investigated.The proposed studies will reveal a variety of atomistic interaction morphologies, characteristics associated with them are expected to provide a necessary connection to experimentally visualized morphologies. The effects of different interaction states on membrane properties could facilitate molecular-level understanding of the cytotoxic effects of nanomaterials. The dynamic and thermodynamic results could uncover molecular mechanisms for coupling behaviors of nanosheets and lipid membranes, and provide biological implications for the mitigation of nanotoxicity.