Exploiting Molecular Complexity to Advance Nanostructural Design

Lead Research Organisation: Imperial College London
Department Name: Life Sciences


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.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509486/1 30/09/2016 30/03/2022
1961334 Studentship EP/N509486/1 29/09/2017 01/12/2020 Carlos Navarro Paya
Description Some molecular dynamics (MD) restraints were designed to improve the behaviour of a specific disordered protein (alpha-synuclein) with the coarse-grained MD forcefield Martini3. Specifically to impose different conformational states relevant to this proteins interaction with lipid membranes. The end goal is to be able to use experimental data to impose exploration of these conformational states accordingly.
Exploitation Route This design to improve the conformational exploration of this specific protein, once finalised, should be able to be used in combination with experimental data, to improve the behaviour of similarly disordered proteins that acquire secondary structure when interacting with membranes.
Sectors Pharmaceuticals and Medical Biotechnology