Computational investigation on lipid bilayer disruption induced by amphiphilic Janus nanoparticles: combined effect of Janus balance and charged lipid concentration.

Janus nanoparticles (NPs) with charged/hydrophobic compartments have garnered attention for their potential antimicrobial activity. These NPs have been shown to disrupt lipid bilayers in experimental studies, yet the underlying mechanisms of this disruption at the particle-membrane interface remain unclear. To address this knowledge gap, the present study conducts a computational investigation to systematically examine the disruption of lipid bilayers induced by amphiphilic Janus NPs. The focus of this study is on the combined effects of the hydrophobicity of the Janus NP, referred to as the Janus balance, defined as the ratio of hydrophilic to hydrophobic surface coverage, and the concentration of charged phospholipids on the interactions between Janus NPs and lipid bilayers. Computational simulations were conducted using a coarse-grained molecular dynamics (MD) approach. The results of these MD simulations reveal that while the area change of the bilayer increases monotonically with the Janus balance, the effect of charged lipid concentration in the membrane is not easy to be predicted. Specifically, it was found that the concentration of negatively charged lipids is directly proportional to the intensity of membrane disruption. Conversely, positively charged lipids have a negligible effect on membrane defects. This study provides molecular insights into the significant role of Janus balance in the disruption of lipid bilayers by Janus NPs and supports the selectivity of Janus NPs for negatively charged lipid membranes. Furthermore, the anisotropic properties of Janus NPs were found to play a crucial role in their ability to disrupt the membrane via the combination of hydrophobic and electrostatic interactions. This finding is validated by testing the current Janus NP design on a bacterial membrane-mimicking model. This computational study may serve as a foundation for further studies aimed at optimizing the properties of Janus NPs for specific antimicrobial applications.