Exploiting Molecular Complexity to Advance Nanostructural Design

理解和控制自组装成纳米结构的分子是当前最大的挑战。更具体地说，由非共价键编织在一起的新分子结构的设计，如超分子水凝胶，而不是由共价键连接的合成凝胶，赋予它们限制其在生物医学领域使用的特性。一些超分子凝胶根据对外界刺激的反应表现出可逆的相变。这些可切换的分子纳米结构有望影响纳米和生物技术领域的下一代材料，因为它们具有广泛的应用范围，从药物输送、生物传感器、生物支架到组织工程和能源细胞。虽然在超分子组件领域已经取得了实质性的进展，但仍然存在一些根本性的挑战，如确定基于理性的特性，如开关机制或组件[2]的最终结构和动力学特性。本提案旨在彻底改变分析方法，将分子自组装设计成复杂的纳米结构，具有良好定义的均匀生化特性，包括新型生物材料和可切换组件。该项目的目的是优化一种强大的多尺度方法，该方法集成了核磁共振实验和分子动力学模拟，将这种方法用于研究大分子纳米结构的自组装、稳定性和可切换性背后的复杂分子相互作用。最初，该方法的两个应用将推动项目的发展。第一个应用将侧重于α -突触核蛋白的生物学过程，α -突触核蛋白是一种神经元蛋白，在突触[2]的突触囊泡运输中起作用，促进突触囊泡和突触蛋白[4]基质的自组装。我们将探讨α -突触核蛋白介导的突触囊泡组装和融合的动力学和机制。第二个应用将侧重于基于主客体相互作用的超分子水凝胶的形成，以及如何表征它们的特性，如形成机制、可切换性、自我修复或形状记忆。总之，我们的目标包括开发和应用先进的多学科方法，以促进我们对分子自组装的理解和控制，这将为下一代生物纳米材料的设计提供知识和工具。[10]邵宇，贾辉，曹涛，刘丹，2017。基于DNA自组装的超分子水凝胶。化学研究，50(4),pp.659-668。[10]董荣，庞勇，苏勇，朱晓明，2015。超分子水凝胶：合成、性质及其生物医学应用。生物材料科学，3(7),pp.937-954。

Understanding and controlling molecules that self-assemble into nanostructures is a top current grand challenge. More specifically, the design of new molecular architectures that are weaved together by non-covalent bonds, such as supramolecular hydrogels, as opposed to synthetic gels which are covalently linked conferring them properties that limit their use in biomedical fields. Some supramolecular gels show reversible phase transitions depending on the response to external stimuli. These switchable molecular nanostructures are expected to impact the next generation of materials in nano- and bio- technologies [2], as they have a wide range of applications ranging from drug delivery, biosensors, bio-scaffolds to tissue engineering and energy cells. Although there has been substantial progress in the area of supramolecular assemblies, there are still fundamental challenges such as the determination of rational-based properties such as the switching mechanisms or the final structural and dynamical characteristics of the assemblies [2]. The present proposal aims at a radical transformation in the analytical approach to design molecular self-assembly into complex nanostructures, with well-defined homogeneous biochemical properties, including novel biomaterials and switchable assemblies. The aim of this project is to optimise a powerful multiscale approach, that integrates NMR experiments and molecular dynamic simulations, tailoring this method to the study of the complex molecular interactions underlying self-assembly, stability and switchability of macromolecular nanostructures.Initially two applications of the method will drive the development of the project. The first application will focus on a biological process by which alpha-synuclein, a neuronal protein that has function in the trafficking of synaptic vesicles at the synapse [2], promotes the self-assembly of a matrix of synaptic vesicles and synaptic proteins [4]. We will look into the dynamics and mechanism of alpha-synuclein mediated assembly and fusion of synaptic vesicles. The second application will focus on the formation of supramolecular hydrogels based on host-guest interactions and how it is possible to characterise their properties such as the mechanism of formation, switchability, self-healing or shape memory.Taken together our aims include the development and application of an advanced multidisciplinary approach to advance our understanding and control of molecular self-assembly, which will generate knowledge and tools toward the design of the next generation of bio-nanomaterials.[1]: Shao, Y., Jia, H., Cao, T. and Liu, D., 2017. Supramolecular Hydrogels Based on DNA Self-Assembly. Accounts of Chemical Research, 50(4), pp.659-668.[2]: Dong, R., Pang, Y., Su, Y. and Zhu, X., 2015. Supramolecular hydrogels: synthesis, properties and their biomedical applications. Biomaterials science, 3(7), pp.937-954.