Molecular Modeling of the Fluorination Effect on the Penetration of Nanoparticles across Lipid Bilayers.

The fluorinated decorations have recently been widely used in many biomedical applications. However, the potential mechanism of the fluorination effect on the cellular delivery of nanoparticles (NPs) still remains elusive. In this work, we systemically explore the penetration of a perfluoro-octanethiol-coated gold NP (PF-Au NP) and, for comparison, an octanethiol-coated gold NP (OT-Au NP) across lipid bilayers. We also investigated the effect of these two types of NPs on the properties of lipid bilayers. Our findings indicate that the lipid type and the surface tension of the lipid bilayer significantly impact the penetration capabilities of the fluorinated gold NP. By examining the distribution of ligands on the surface of the two types of NPs in water and during the penetration process, we unveil their distinct penetration characteristics. Specifically, the PF-Au NP exhibits amphiphobic behavior (both hydrophobic and lipophobic), while the OT-Au NP exhibits solely hydrophobic characteristics. Finally, we observe that the penetration capabilities can be increased by adjusting the degree of fluorination of the ligands on the NP surface. Overall, this study provides useful physical insights into the unique properties of the fluorinated decorations in NP permeation.

Molecular Simulation Studies on the Interactions of Bilirubin at Different States with a Lipid Bilayer.

The unconjugated bilirubin (BR) may penetrate through the cell membrane and cause a severe cytotoxicity. However, the molecular mechanism underlying the penetration of BR into the cell membrane is still largely unknown. In this work, we systematically investigate the interaction of BR and a lipid bilayer under different conditions by using all-atom molecular dynamics simulations. It is found that BR at the Z,Z conformation can easily enter into the interior of the lipid bilayer due to its hydrophobicity. However, when BR transforms from the Z,Z conformation to the E,E conformation (after the blue-light emission), its penetration ability is greatly reduced (especially at its ionized state). This study may offer useful physical insights into the effect of phototherapy on the penetration behavior and the cytotoxicity of the unconjugated BR.

Controlling the Interaction of Nanoparticles with Cell Membranes by the Polymeric Tether.

The well control over the cell-nanoparticle interaction can be of great importance and necessity for different biomedical applications. In this work, we propose a new and simple way (i.e., polymeric tether) to tuning the interaction between nanoparticles and cell membranes by dissipative particle dynamics simulations. It is found that the linked nanoparticles (via polymeric tether) can show some cooperation during the cellular uptake and thereby have a higher wrapping degree than the single nanoparticle. The effect of the property of the polymer on the wrapping is also investigated, and it is found that the length, rigidity, and hydrophobicity of the polymer play an important role. More interestingly, the uptake of linked nanoparticles could be adjusted to the firm adhesion via two rigid polymeric tethers. The present study may provide some useful guidelines for novel design of functional nanomaterials in the experiments.