Exploiting Molecular Complexity to Advance Nanostructural Design

利用分子复杂性推进纳米结构设计

• 批准号: 1961334
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1961334
• 关键词: Exploiting; Molecular; Complexity; Advance; Nanostructural

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.

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，设计通过非共价键编织在一起的新分子结构，如超分子水凝胶，而不是共价连接的合成凝胶，赋予它们限制其在生物医学领域中使用的性质。一些超分子凝胶表现出可逆的相变，这取决于对外界刺激的响应。这些可切换的分子纳米结构预计将影响纳米和生物技术中的下一代材料[2]，因为它们具有广泛的应用范围，从药物递送，生物传感器，生物支架到组织工程和能量电池。虽然在超分子组装领域已经取得了实质性的进展，但仍然存在基本的挑战，例如确定基于理性的性质，例如组装体的开关机制或最终结构和动力学特性[2]。本提案的目的是在分析方法中进行根本性的转变，以设计分子自组装成复杂的纳米结构，具有明确的均匀生物化学性质，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，该方法将NMR实验和分子动力学模拟相结合，使该方法适合于研究大分子纳米结构的自组装、稳定性和可切换性等复杂分子相互作用。最初，该方法的两个应用将推动该项目的发展。第一个应用程序将集中在生物过程中，α-突触核蛋白，神经元蛋白，具有在突触的突触囊泡的运输功能[2]，促进突触囊泡和突触蛋白基质的自组装[4]。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。第二个应用将重点关注基于主客体相互作用的超分子水凝胶的形成，以及如何表征其性质，例如形成机制、可转换性、自愈或形状记忆。总而言之，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，这将为设计下一代生物纳米材料提供知识和工具。[1]：Shao，Y.，贾，H.，Cao，T.和Liu，D.，2017.基于DNA自组装的超分子水凝胶。化学研究帐户，50（4），第659 -668页。[2]：Dong，R.，彭，Y.，Su，Y.和Zhu，X.，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），第937 -954页。