两亲性短肽的细胞内自组装研究

将分子自组装研究由体外简单溶液扩展到细胞内部进行，有利于人们正确认识真实生理条件下分子的自组装行为及其组装过程调控，并与其生物学功能建立直接的联系。基于此，本项目拟开展两亲性短肽的细胞内自组装研究。通过合理的分子设计得到含有两亲性短肽自组装基元的前体分子，这些分子在细胞外无法组装，而当其进入到细胞内部后，在特定酶的作用下酶解释放出短肽自组装基元，从而触发自组装过程；优化分子的细胞内输运途径，考察短肽向细胞内的转移过程和机制；对比考察两亲性短肽在胞外及胞内自组装行为的异同，明确短肽在细胞内的自组装结构及其在细胞内的定位；认识短肽胞内转移和自组装的细胞选择性，评价其对细胞生理活性的影响，建立胞内组装体结构与其特定生物功能的直接联系。项目有望在以生物学功能为导向的分子自组装体系设计和组装过程调控方面取得重要进展。

To expand the molecular self-assembly research from in vitro simple solutions to cells can help to understand the exact in vivo self-assembly behaviors as well as to control the assembly process.It is also helpful to estabilish the direct correlation between the molecular self-assembly behaviors and the biological functions. Therefore, the program proposes to study the self-assembly of short amphiphilic peptides inside the cells. The functional molecular precusors are obtained by rational molecular design. These precusors do not self-assemble into distinct structures outside cells, while they would be lysed to release the self-assembling peptide units and start to self-assemble when they are transferred into the cells. The transfer process and mechanism of the precusors into the cells will be investigated to optimize the transfering routes. The self-assembly of the peptides outside the cells and inside the cells will be studied and compared with each other. The self-assembled structures and the locations of them inside cells will be characterized aiming to know the in vivo self-assembly process and the mechanism. The cell selectivity of the peptide transfer and self-assembly as well as their effects on the cellular biological activity will also be investigated and evaluated, trying to estabilsh the direct correlation between the self-assembled structures and the specific biological functions. The project is innovative and hopeful to make exciting progress in the development of biological function oriented self-assembly systems.