多组分脂质体—纳米粒进入巨型囊泡的跨膜运输研究

发布时间：2018-05-03 00:37

本文选题：多组分脂质体-纳米粒 + 巨型囊泡　；参考：《山西师范大学》2017年硕士论文

【摘要】：多组分脂质体-纳米粒是一种新颖的基因载体,是由一定浓度的多组分脂质体囊泡和纳米粒分散在溶液中自组装形成的具有纳米粒核心和脂质外壳的新型组装体,内部的核由聚合物组成,相当于一个纳米粒子,外部的壳由脂质层组成。多组分脂质体-纳米粒载体可将目的基因送入靶细胞内,然后将目的基因释放出来,在生物医学的基因治疗领域是很受欢迎的。巨型囊泡是卷成球壳的脂质双层,被广泛用于研究脂质双层的性质。本文使用自洽场理论对多组分脂质体-纳米粒进入巨型囊泡的跨膜运输进行了研究。第一章,介绍了细胞膜的组成功能和特性,人工合成膜,多组分脂质体-纳米粒的结构、制备及应用以及纳米粒与生物膜的作用方式,同时介绍了在细胞膜体系中自洽场理论模型的应用。本文采用自洽场方法来研究细胞膜的自组织行为。第二章,对单个多组分脂质体-纳米粒进入巨型囊泡膜的跨膜运输进行了研究。讨论了在内吞过程中,多组分脂质体的头体积分数和纳米粒的半径对膜形貌变化的影响,还研究了在准静态下能量壁垒的不同。当脂质种类A和B的头体积分数(f_(h A),f_(h B))相同时,得到亚稳中间体IMI相,H_(II)相,stalk相和HD相,而当脂质种类A和B的头体积分数不同时,形成了亚稳中间体stalk相,IMI相,SUV相,H_(II)相和HD相。然而,纳米粒的半径(R_p)对膜形貌的影响很小。我们运用自由能曲线定量分析了最小自由能路径。通过比较自由能,最优参数结合是f_(h A)=f_(h B)=0.2,f_(h A)=0.2,f_(h B)=0.55,R_p=0.35R_g。结果表明,单个多组分脂质体-纳米粒与巨型囊泡的相互作用是一个自发过程,并且在相互作用的过程中,形成亚稳中间体时需要克服能量壁垒。第三章,对多个多组分脂质体-纳米粒进入巨型囊泡膜的跨膜运输进行了研究。讨论了在内吞过程中,多组分脂质体-纳米粒的个数和多组分脂质体-纳米粒的聚集形式对膜形貌变化的影响,还研究了在准静态下能量壁垒的不同。我们运用自由能曲线定量分析了最小自由能路径。分析自由能曲线表明,多个多组分脂质体-纳米粒与巨型囊泡的相互作用是一个自发过程,并且在相互作用的过程中,形成亚稳中间体时需要克服能量壁垒。第四章,对多组分脂质体-纳米粒进入巨型囊泡膜的跨膜运输研究进行了总结。
[Abstract]:Multicomponent liposome-nanoparticle is a novel gene carrier. It is a new type of assembly with nanoparticles core and lipid shell which is composed of multi-component liposome vesicles and nanoparticles dispersed in solution. The inner nucleus consists of a polymer, which is equivalent to a nanometer particle, and the outer shell is composed of a lipid layer. Multicomponent liposome-nanoparticles vector can transfer the target gene into the target cells and then release the target gene, which is very popular in the field of biomedical gene therapy. Giant vesicles are bilayer lipids rolled into spherical shells, which are widely used to study the properties of lipid bilayers. In this paper, the transmembrane transport of multicomponent liposomes into giant vesicles was studied by using self consistent field theory. In the first chapter, the composition and characteristics of cell membrane, the synthetic membrane, the structure of multicomponent liposome and nanoparticles, the preparation and application, and the interaction between nanoparticles and biofilm are introduced. At the same time, the application of self-consistent field theory model in cell membrane system is introduced. Self-organizing behavior of cell membrane is studied by self-consistent field method. In chapter 2, the transmembrane transport of single multicomponent liposome-nanoparticles into giant vesicle membrane was studied. The effects of the head volume fraction of multicomponent liposomes and the radius of nanoparticles on the changes of membrane morphology during the process of endocytosis were discussed. The differences of energy barriers in quasi-static state were also studied. When the head volume fraction of lipids A and B is the same, the metastable intermediates IMI phase and IMI phase are obtained. When the head volume fraction of lipid species A and B is different, the metastable intermediates, stalk phase, IMI phase, SUV phase, and HD phase, are obtained. However, the radius of nanoparticles has little effect on the morphology of the film. We use the free energy curve to quantitatively analyze the minimum free energy path. By comparing the free energy, the best parameter combination is: the number of A)=f_(h is 0.2g / s. The results show that the interaction between single multicomponent liposome-nanoparticles and giant vesicles is a spontaneous process, and in the process of interaction, energy barriers should be overcome in the formation of metastable intermediates. In chapter 3, the transmembrane transport of multi-component liposomes-nanoparticles into giant vesicles was studied. The effects of the number of multicomponent liposome-nanoparticles and the aggregation form of multicomponent liposome-nanoparticles on the morphology of the membrane were discussed in the process of endocytosis. The differences of energy barriers in quasi-static state were also studied. We use the free energy curve to quantitatively analyze the minimum free energy path. The free energy curves show that the interaction between multi-component liposome-nanoparticles and giant vesicles is a spontaneous process, and energy barriers should be overcome in the process of forming metastable intermediates. In chapter 4, the transmembrane transport of multicomponent liposomes-nanoparticles into giant vesicles was summarized.
【学位授予单位】：山西师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1

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