不对称超支化聚合物囊泡的制备及其可控出芽研究

To know the organization structure and biological function of biological membrane from the molecular level has been explored by scientist for many years. Simplified cells into vesicles, simulating some complex life process of the cell membrane, is the study means of cell bionics. As a new kind of assemblies, branched polymersomes process the combined properties, such as good membrane fluidity and strong stability, of liposomes and polymersomes, and have demonstrated the potential to be excellent model membranes for mimicking cellular function. In our previous studies, branched polymersomes have been used to mimick celluar fusion, fission, and aggregation process, and many significant results have been achieved. However, an excellent model membrane should have the functions of asymmetry and controlled deformations. How to introduce these concepts into the branched polymersomes is the key of our model membranes preparing. Therefore, we put forward our project with the following objectives: 1) Preparing a new kind of stimulus-responsive asymmetric two-component branched polymersomes , and the fluidity and asymmetry of the polymersome are investigated; 2) The branched polymersome is induced to bud by environmental change. The relation between the change and bud number and size are constructed to achieve controllable budding.3) The theoretical and experimental research is carried out to investigate the budding mechanism, and the results provide theoretical basis for the branched polymersomes being excellent model membranes.

从分子水平认识生物膜的组织结构及生物功能是科学家们不断探索的内容。将细胞简化为囊泡，模拟细胞膜上一些复杂的生命过程，是细胞仿生学的研究手段。作为一种新型的组装体，超支化囊泡结合了脂质体囊泡和聚合物囊泡性能特点，如好的流动性和高的稳定性，在细胞膜的功能模拟中具有广阔的前景。前面的工作中，我们已将超支化聚合物囊泡应用于细胞膜融合、分裂及聚集等性能的模拟，取得了较好的效果。但是，作为一种细胞模型薄膜，还应具有不对称、变形可控等性能。如何将这些概念引入超支化囊泡，是我们制备模型薄膜的关键所在，为此提出本项目的申请：1) 制备一种刺激响应性双组分超支化囊泡，并对其不对称性、流动性等进行探讨；2) 通过环境的改变，诱导囊泡出芽，建立环境变化与囊泡芽体大小、数量等变形性能的关联，实现囊泡出芽的可控性；3) 对囊泡出芽机理进行理论模拟和实验探讨，为其成为理想的细胞模型薄膜提供进一步的理论依据。

从分子水平上认识生物膜的组织结构及生物功能一直是科学家们不断努力探索的内容。将细胞简化为囊泡，模拟细胞膜上一些复杂的生命过程，是细胞仿生学的研究手段。作为一种新型的组装体，超支化聚合物囊泡BP结合了脂质体囊泡和聚合物囊泡性能特点，如好的膜流动性和高的稳定性，在细胞膜的功能模拟中具有广阔的前景。在前面的工作中，我们已将超支化聚合物囊泡应用于模拟细胞膜融合、分裂以及粘合等性能的研究，取得了较好的效果。但是，作为一种细胞模型薄膜，还应该具有不对称、变形可控等性能特点。.本项目中，我们利用超支化聚合物HBPO-star-PEO和HBPO-star-PDMAEMA相同核心的锚定作用制备得到多功能化刺激响应性复合囊泡BPD，其具有可控不对称性以及较好膜流动性。改变两者的比例，BPD囊泡的尺寸可控地在纳米级到微米级之间变化，尺寸的可调节性赋予其广泛的应用前景。HBPO-star-PDMAEMA囊泡具有pH响应性，体系中加入稀硝酸水溶液后，BPD囊泡发生破裂、翻转以及出芽等形变。显微镜下实时跟踪发现囊泡出芽经历以下过程：(1) 囊泡边沿褶皱的形成；(2) 芽体的出现；(3) 芽体长大；(4) 芽体之间的融合；(5) 芽体的消失。用稳态荧光淬灭法对囊泡出芽机理进行了初步探讨，结果表明，形变是由囊泡内外层分子的flip-flop翻转运动、内外层面积差改变以及囊泡内外pH阶等共同作用下产生的。这与生物体内细胞胞吞、物质传送及交换等特异性形变过程相似，因而BPD囊泡可以用来研究细胞出芽和分离机制，为其成为更加理想的细胞模型薄膜提供进一步的理论依据。