Membrane-Mediated Interactions between Anisotropic Nanoparticles

纳米粒子在许多生物医学应用中具有巨大的潜力，包括生物传感、诊断、基因治疗、药物递送、磁热疗和光热治疗。然而，也存在与许多类型的纳米颗粒的潜在环境和健康危害相关的担忧。纳米颗粒的生物医学应用及其潜在毒性需要它们粘附在包裹活细胞的薄包膜上，称为质膜，并最终进入细胞。主要由脂质组成的质膜是所有活细胞的重要组成部分。它是流体和高度灵活的。结果，纳米颗粒的粘附导致质膜的变形，这又导致纳米颗粒的聚集。 虽然已经研究了脂质膜对球形纳米颗粒聚集的影响，但仍然缺乏对脂质膜对具有复杂几何形状或表面性质的纳米颗粒之间的相互作用及其产生的聚集的影响的理解。尽管具有复杂几何形状或表面性质的纳米颗粒比球形纳米颗粒具有更有前途的生物医学应用。该项目旨在了解膜对具有复杂几何形状或表面性质的纳米颗粒之间相互作用的影响。在这项研究的过程中，首席研究员将培训研究生和本科生在各种计算方法，这将为他们在干领域的职业生涯做好准备。 高中生还将通过孟菲斯大学物理与材料科学系举办的暑期项目参与研究的某些方面。该研究的各个方面将被整合到由首席研究员教授的本科生和研究生水平的一些课程中。技术总结该奖项支持对由纳米颗粒粘附在脂质膜上导致的膜变形引起的各向异性纳米颗粒的两体相互作用和自组装的研究。这项研究将通过对一个有效的粗粒度模型进行系统的大规模分子动力学模拟来进行。这种方法的效率源于对溶剂的隐式处理，软化珠粒之间的成对相互作用，以及将纳米颗粒处理为中空镶嵌表面。两种主要类型的各向异性纳米粒子，相应的球柱纳米粒子和Janus纳米粒子，将被认为是在这项研究中。在所提出的研究的第一部分中，各向异性纳米颗粒和二聚化模式之间的二聚化阈值将被系统地确定为纳米颗粒的几何形状及其表面异质性的函数。纳米颗粒的二聚化模式将在平面无张力脂质膜的情况下和无张力圆柱形膜和封闭囊泡的情况下进行研究，其中纳米颗粒粘附在膜的内侧或外侧。 在第二部分的研究中，多体效应和自组装的各向异性纳米粒子将被调查的球柱纳米粒子和Janus纳米粒子的不同参数和不同的值的粘附强度。自组装的稳定性将通过自由能计算结果与Helfrich Hamiltonian相结合进行研究。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估而被认为值得支持。

NONTECHNICAL SUMMARYNanoparticles have great potential in many biomedical applications including biosensing, diagnostics, gene therapy, drug delivery, magnetic hyperthermia and photothermal therapy. There are, however, also concerns associated with potential environmental and health hazards of many types of nanoparticles. Biomedical applications of nanoparticles and their potential toxicity necessitate their adhesion on a thin envelope encapsulating living cells known as the plasma membrane, and eventually their cellular entry. The plasma membrane, which is mainly composed of lipids, is an important component of all living cells. It is fluid and highly flexible. As a result, the adhesion of nanoparticles leads to deformation of the plasma membrane, which in turn leads to the aggregation of nanoparticles. While there have been studies on the effect of lipid membranes on the aggregation of spherical nanoparticles, the understanding of the effect of lipid membranes on interactions between nanoparticles with complex geometries or surface properties, and their resulting aggregation, remains lacking. This is despite nanoparticles with complex geometries or surface properties having more promising biomedical applications than spherical ones. This project aims at understanding the effect of membranes on interactions between nanoparticles with complex geometries or surface properties. During the course of this research, the principal investigator will train graduate and undergraduate students in various computational approaches, which will prepare them for careers in STEM fields. High school students will also be engaged in some aspects of the research through a summer program run by the Department of Physics and Materials Science at the University of Memphis. Aspects of the research will be integrated is some courses at the undergraduate and graduate levels that are taught by the principal investigator.TECHNICAL SUMMARYThis award supports an investigation of the two-body interaction and self-assembly of anisotropic nanoparticles induced by membrane deformations resulting from nanoparticles’ adhesion on lipid membranes. The research will be carried out through systematic and large-scale molecular dynamics simulations of an efficient coarse-grained model. The efficiency of this approach stems from the treatment of the solvent implicitly, softening the pair-wise interactions between beads, and the treatment of the nanoparticles as hollow tessellated surfaces. Two main types of anisotropic nanoparticles, corresponding to sphero-cylindrical nanoparticles and Janus nanoparticles, will be considered in this research. In the first part of the proposed research, the dimerisation threshold between anisotropic nanoparticles and the modes of dimerisation will be determined systematically as a function of the geometry of the nanoparticles and their surface heterogeneities. The modes of dimerisation of the nanoparticles will be investigated both in the case of planar tensionless lipid membranes and in the case of tensionless cylindrical membranes and closed vesicles, with the nanoparticles adhering either to the inner or outer side of the membrane. In the second part of the research, multi-body effects and self-assembly of the anisotropic nanoparticles will be investigated for varying parameters of the sphero-cylindrical nanoparticles and Janus nanoparticles and for varying values of the adhesion strength. The stability of the self-assemblies will be investigated by free-energy calculations of the results in conjunction with the Helfrich Hamiltonian.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.