Computational investigation on lipid bilayer disruption induced by amphiphilic Janus nanoparticles: combined effect of Janus balance and charged lipid concentration
Computational investigation on lipid bilayer disruption induced by amphiphilic Janus nanoparticles: combined effect of Janus balance and charged lipid concentration
复制标题
两亲性 Janus 纳米粒子诱导的脂质双层破坏的计算研究：Janus 平衡和带电脂质浓度的综合影响
作者：
Nguyen, Danh;Wu, James;Corrigan, Patrick;Li, Ying
具有带电/疏水区室的Janus纳米颗粒（NP）因其潜在的抗微生物活性而引起关注。在实验研究中，这些纳米颗粒已被证明可以破坏脂质双层，但在颗粒-膜界面处这种破坏的潜在机制仍不清楚。为了解决这一知识差距，本研究进行了计算调查，系统地检查两亲性Janus纳米粒子诱导的脂质双层的破坏。本研究的重点是Janus NP的疏水性的组合效应，称为Janus平衡，定义为亲水性与疏水性表面覆盖率的比率，以及带电磷脂的浓度对Janus NP和脂质双层之间的相互作用。使用粗粒度的分子动力学（MD）方法进行了计算模拟。这些MD模拟的结果表明，虽然双层的面积变化单调增加的Janus平衡，在膜中的带电脂质浓度的影响是不容易预测的。具体地，发现带负电荷的脂质的浓度与膜破坏的强度成正比。相反，带正电荷的脂质对膜缺陷的影响可以忽略不计。这项研究提供了分子的Janus平衡的显着作用的Janus纳米颗粒的脂质双层的破坏和支持的选择性Janus纳米颗粒带负电荷的脂质膜。此外，Janus NPs的各向异性特性被发现在其通过疏水和静电相互作用的组合破坏膜的能力中起着至关重要的作用。通过在细菌膜模拟模型上测试当前Janus NP设计来验证这一发现。这种计算研究可以作为进一步研究的基础，旨在优化Janus NPs的特性，用于特定的抗菌应用。
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.