Institute of Nanotechnology for Single Cell Analysis (INSCA), Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100191, China.
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing 210096, China.
Nanoscale. 2020 Feb 14;12(6):4101-4109. doi: 10.1039/c9nr09226a. Epub 2020 Feb 5.
Due to different interactions between lipids and proteins, a plasma membrane can segregate into different membrane domains. Among them, ordered functional membrane domains are defined as "lipid rafts", which play key roles in many biological processes (e.g., signal transduction, endocytosis, etc.) in the cell. Hence, it will be of much biological significance to monitor and even regulate the dynamics of lipid rafts. In this work, we designed a ligand-modified spherical nanoparticle with coarse-grained molecular dynamics simulations, which can be encapsulated into the hydrophobic region of the lipid membrane and specifically target either raft or non-raft membrane domains. The preferred localization of the nanoparticle can be tuned by adjusting ligand hydrophobicity, length and density. Generally, more hydrophobic nanoparticles tend to target the raft domain, while less hydrophobic nanoparticles prefer the non-raft domain. Besides, ligand length and density jointly determine the exposure of nanoparticle cores and thus affect the roles of ligands in nanoparticles' final localization. Our results may provide insights into the experimental design of functional nanoparticles, targeting the lipid raft and regulating its dynamics.
由于脂质和蛋白质之间的相互作用不同，质膜可以分成不同的膜域。其中，有序的功能性膜域被定义为“脂筏”，它在细胞的许多生物过程（如信号转导、内吞作用等）中起着关键作用。因此，监测甚至调节脂筏的动力学将具有重要的生物学意义。在这项工作中，我们设计了一种配体修饰的球形纳米颗粒，通过粗粒化分子动力学模拟，可以将其包裹在脂质膜的疏水区，并特异性地靶向筏或非筏膜域。通过调节配体疏水性、长度和密度，可以调整纳米颗粒的优先定位。一般来说，疏水性更强的纳米颗粒更倾向于靶向筏域，而疏水性较弱的纳米颗粒则更倾向于非筏域。此外，配体长度和密度共同决定了纳米颗粒核心的暴露程度，从而影响配体在纳米颗粒最终定位中的作用。我们的研究结果可能为靶向脂筏并调节其动力学的功能纳米颗粒的实验设计提供了新的思路。
