Temperature-Dependent Lipid Extraction from Membranes by Boron Nitride Nanosheets

Abstract

Two-dimensional (2D) materials can mechanically insert into cell membranes and extract lipids out, thus leading to the destruction of cell integrity. On the one hand, the cytotoxicity of 2D materials can be harnessed in surface engineering to resist biofouling, and on the other hand, it causes great concern with in vivo biomedical applications ranging from drug delivery to nanoimaging. To understand the nature of this cytotoxic behavior and find strategies to control it, we performed molecular dynamics (MD) simulations on the lipid extraction of hexagonal boron nitride (BN) nanosheets from lipid membranes. Interestingly, we observed that the lipid extraction behavior suddenly disappears as temperature decreases. Structural analyses revealed that this temperature dependence is related to the lipid membrane phase transition, which was confirmed by an additional membrane model with phase state regulated by cholesterol. The potential of mean force calculation was adopted to clarify the thermodynamic origin of these results, which also indicates directions to adjust the lipid extraction behavior of nanomaterials. Overall, this work suggests that the cytotoxic mechanical interactions between 2D materials and cell membranes can be controlled by temperature and other factors which can induce phase transitions of lipid membranes and that the thermodynamic threshold of the lipid extraction varies for surfaces with different curvature. This work clarifies the thermodynamics in the lipid extraction phenomenon of 2D materials and indicates possible strategies to adjust the antibacterial performance or cytotoxicity of 2D materials.

Superior Compatibility of C2N with Human Red Blood Cell Membranes and the Underlying Mechanism

“…It is interesting to note that a recent mechanism study by Fan and coworkers showed that the lipid extraction from cell membranes by BN nanosheets is temperature dependent: the lipid extraction behavior can emerge at higher temperatures due to a phase transition occurring in the lipid membrane, thereby inducing the cytotoxicity of the nanosheets . Herein, we also examined whether this temperature‐dependent lipid extraction behavior is also present in the case of C 2 N. A set of additional three independent simulations based on the initial system of C 2 N–POPC extraction simulations were performed at a higher temperature 310 K with each running for 300 ns.…”

2D-enabled membranes: materials and beyond

“…h-BN is an attractive 2D material for membrane applications owing to its unique and excellent properties such as high strength, insulation, thermal stability and conductivity and chemical inertness [111][112][113]. Those properties make it promising, but its extremely high chemical inertness has restricted its wide-spread application.…”

Modeling Interactions between Liposomes and Hydrophobic Nanosheets

“…To avoid the effect of sharp edges and corners of nanosheets as reported previously, rounded nanosheet models with smooth edges were used. In previous simulation studies, the size of nanosheet models was usually comparable with membrane thickness (several nanometers) . However, nanosheets in experiments are much larger, and the size of nanosheets can be several hundreds (and even thousands) of nanometers .…”

“…First, lipids in the liposome are extracted out under van der Waals attraction and hydrophobic interaction as reported by Tu et al Then, the climbing of lipids drags nanosheets toward the opposite direction, and nanosheets insert into the lipid membrane. In our previous work, we found that the lipid extraction behavior depends on temperature and other factors that could lead to the phase transition of lipid membranes. Strategies to tune the lipid extraction behavior proposed in previous work could be used to prevent the formation of these destructive interaction states.…”

“…In our previous work, we found that the lipid extraction behavior depends on temperature and other factors that could lead to the phase transition of lipid membranes. Strategies to tune the lipid extraction behavior proposed in previous work could be used to prevent the formation of these destructive interaction states. The lipid extraction is a general behavior of different hydrophobic nanosheets such as graphene, graphyne, graphene oxide, and boron nitride nanosheets.…”