针对耐药菌及病毒感染、肿瘤、自体免疫性疾病等健康威胁,致力于从生物物理的角度,以纳米-细胞膜界面为研究核心,结合先进的实验技术、机器学习和分子模拟方法,发展新的研究手段、揭示纳米物质与生物体系的界面相互作用分子机制,设计精准靶向纳米药物及载体。主要研究内容包括:
(1)发展纳米-细胞膜界面问题研究的实验及理论模拟研究方法,实现对细胞膜界面非平衡动力学过程在分子层面上的精准分析;
(2)以生物肽、脂质体、纳米材料等为基础,发展基于生物界面调控的智能性抗耐药菌、抗病毒、抗肿瘤、免疫干涉药物;
(3)高通量筛选疾病生物标记物及靶向配体,实现细胞膜精准靶向药物递送;
(4)AI辅助的临床数据分析及精准医疗。
近期主要研究内容:
【4】筛选疾病生物标记物和靶向配体;AI辅助多肽设计、临床数据分析及精准医疗
(AI辅助多肽设计)Assembly-Induced Membrane Selectivity of Artificial Model Peptides through Entropy−Enthalpy Competition, ACS Nano, 18, 28, 18650, 2024.
(AI辅助材料设计)Machine-Assisted Inverse Design of Patchy Particles for Self-Assembly of Complex Interfacial Tessellations, under review
(AI辅助实验室数据分析)基于无监督学习方法的细胞膜内单分子扩散运动分析:胆固醇对模型膜和活细胞膜流动性的不同影响,物理学报, 73(18), 188702, 2024. (封面文章)
(AI辅助临床数据分析)[红斑狼疮AI医学助手v1.0]
在研项目“靶向脑胶质瘤脂质纳米颗粒载体设计及核酸递送应用研究”
在研项目“基于纳米-细胞界面蛋白质组的巨胞饮作用分子机制研究” (负责人:魏裕双)
【3】靶向细胞膜的多肽类纳米药物及脂质纳米粒载体设计:抗菌/抗肿瘤/免疫调控
Helicity-directed recognition of bacterial phospholipid via radially amphiphilic antimicrobial peptides, Sci. Adv., 10, eadn9435, 2024.
A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens, NPG Asia Mater., 13, 18, 2021.
Membrane perturbation of fullerene and graphene oxide distinguished by pore-forming peptide melittin, Carbon, 180, 67-76, 2021.
Graphene oxide as antibacterial sensitizer: mechanically disturbed cell membrane for enhanced poration efficiency of melittin, Carbon, 149, 248-256, 2019.
Designing Melittin-Graphene Hybrid Complexes for Enhanced Antibacterial Activity, Adv. Healthc. Mater., 1801521, 2019.
在研项目“多肽抗菌复合体:空间微结构调制及分子作用机理”
在研项目“脂质-纳米结构杂合体系的组装机制、结构性能表征及应用” (已结题)
【2】(纳米粒、脂质体)-细胞膜界面作用机制研究
Membrane-specific binding of 4 nm lipid nanoparticles mediated by an entropy-driven interaction mechanism, ACS Nano, DOI: 10.1021/acsnano.2c04774, 2022.
Nanomolar LL-37 induces permeability of a biomimetic mitochondrial membrane, Nanoscale, 14, 17654-17660, 2022
Membrane-curvature-mediated co-endocytosis of bystander and functional nanoparticles, Nanoscale, 13, 9626-9633, 2021.
Cardiolipin Selectively Binds to the Interface of VsSemiSWEET and Regulates Its Dimerization, J. Phys. Chem. Lett., 12, 1940-1946, 2021.
Controlling the Nanoscale Rotational Behaviors of Nanoparticles on the Cell Membranes: A Computational Model, Small, 12(9), 1140-1146, 2016.
在研项目“力信号与生化信号协同调制免疫细胞两个关键界面过程的生物物理研究”
在研项目“功能化纳米颗粒介导的细胞伴吞作用机制研究” (负责人:魏裕双)
【1】发展纳米-细胞膜界面问题研究的实验及模拟研究方法:单脂分子追踪分析技术;光电压界面分析技术
(a) Cholesterol Depletion and Membrane Deformation by MeβCD, and the Resultant Enhanced T Cell Killing, ACS Appl. Mater. Interfaces, 2024 (dynamic GUV leakage assay,定量+实时,表征细胞膜结构变化)
(b) Asymmetric Disturbance and Permeabilization of Bilayer Membranes by 3-nm Carbon Dots, J. Hazard. Mater., 465, 133382, 2024.(使用了多种细胞膜结构表征技术,包括:dynamic GUV leakage ,实时监测膜张力和膜透化;Synchrotron XRD, 测膜xy面内的lipid排布有序性和z方向有序性;QCM-D ,实时监测双叶不对称变化;光电压,膜电学性质变化;MD模拟,提供分子细节、能量计算;等)
(c) Transition between different diffusion modes of individual lipids during the membrane-specific action of As-CATH4 peptides, Small, 2301713, 2023. (单脂分子追踪+非高斯性分析)
(d) Non-Gaussian Diffusion of Individual Lipids Unveils the Unique Peptide–Membrane Interaction Dynamics, J. Phys. Chem. Lett., 14, 854-862, 2023.
(e) Correlation between single-molecule dynamics and biological functions of antimicrobial peptide melittin, J. Phys. Chem. Lett., 11, 4834-4841, 2020.
(f) 综述《光电压瞬态技术:实时分析膜界面动态过程的新手段》,物理学报, 2024, doi: 10.7498/aps.73.20241093