Liu Yue, Zou Guijin, Gao Huajian
School of Engineering, Brown University, Providence, Rhode Island 02912, United States.
Institute of High Performance Computing, A*STAR, Singapore 138632, Singapore.
ACS Nano. 2021 Jan 26;15(1):604-613. doi: 10.1021/acsnano.0c06057. Epub 2021 Jan 6.
Recent experiments have shown that certain molecular agents can selectively penetrate and aggregate in bacterial lipid membranes, leading to their permeability and rupture. To help reveal and understand the underlying mechanisms, here we establish a theory to show that the deformation energy of the membrane tends to limit the growth of molecular domains on a lipid membrane, resulting in a characteristic domain size, and that the domain aggregation significantly reduces the energy barrier to pore growth. Coarse-grained molecular dynamics simulations are performed to validate such domain aggregation and associated pore formation. This study sheds light on how lipid membranes can be damaged through molecular domain aggregation and contributes to establish a theoretical foundation for the next-generation membrane-targeting nanomedicine.
最近的实验表明，某些分子试剂能够选择性地穿透并聚集在细菌脂质膜中，导致其通透性增加并破裂。为了帮助揭示和理解其潜在机制，我们在此建立了一种理论，表明膜的变形能倾向于限制脂质膜上分子域的生长，从而产生特征性的域大小，并且域聚集显著降低了孔生长的能垒。进行了粗粒度分子动力学模拟以验证这种域聚集和相关的孔形成。这项研究阐明了脂质膜如何通过分子域聚集而受损，并有助于为下一代膜靶向纳米医学建立理论基础。
