PhD Studentship in Biomimetic Colloid Science

水溶液中大分子之间的相互作用是一种复杂的现象，它支配着许多重要的化学和生物过程。例如，蛋白质分子间的相互作用决定了它们的时空分布，如簇的形成、聚集和液-液相分离。虽然蛋白质表面非极性残基的百分比可能高达70%，但细胞内蛋白质的浓度保持在极高的水平，即高达40%的体积分数。相比之下，由于各种吸引人的相互作用和库仑排斥的电解液屏蔽，大多数合成胶体系统在如此高的浓度下沉淀。在水基化学和生物环境中，最重要的作用力之一是疏水相互作用，如脂类双层组织和蛋白质折叠。尽管在生物纳米界面上至关重要，但它的基本原理还没有完全被理解。在我们团队中，我们开发了一个模块化平台，其基础是用不稳定的封端剂合成纳米金，然后用指定的目标硫醇配体混合物进行官能化。这种方法不仅适用于具有可调配位体壳层的定制纳米胶体，而且由于Au核显著的散射长度密度，还提供了用小角X射线散射(SAXS)来研究胶体现象的方法。然后，所获得的散射分布可用于通过机器学习算法(协作执行)来提取胶体相互作用项。在一些前期工作的基础上(并结合补充技术)，这个模型系统提供了独特的机会来揭示自然界中发现的胶体现象，这些现象不仅与基础科学有关，而且还与各种工业应用(如药物输送、生物传感、食品科学和个人护理)有关。该项目将以这些初步研究为基础，建立一种综合的合成和分析方法来模拟自然界中发现的胶体相互作用，并揭示其不同寻常的性质。为此，工作将分4个阶段进行：阶段1.平台开发(1-12月)。VIVA升级前的第一年将专门用于平台开发，即合成具有低分散性、核尺寸可调和配基壳层可调的合适的金纳米颗粒-用SAXS研究胶体稳定性-实施机器学习算法以使用高级模型解释SAXS数据(扩展的DLVO理论)培训将至关重要，并将与合作者(数据科学：Keith Butler博士，QMUL；SAXS：Stefan Förster教授)以及参加夏季/冬季学校与社区互动。这一阶段将随着升级viva的起草和辩护而完成。阶段2.了解蛋白质的溶解度(13-24个月)。在阶段1中获得的知识将有助于通过匹配大小和配基组成来创建对天然蛋白质的精确模拟。两亲性分子将作为亲水性分子，以研究胶体稳定性的关键因素，并将这些因素用于金纳米颗粒溶解度的新记录。这些发现将用于与计算同事的合作，比如约克大学的清水诚志博士。阶段3.触发分子识别现象(25-36个月)。目前预计PHD的最后实验阶段将用于研究自然环境中的分子识别。本文开发的实验工具包将用石英晶体微天平和耗散监测对界面吸附现象的研究进行补充。预计将与我所在团队的其他博士研究产生协同效应，例如自动化和高通量表征。

The interactions between macromolecules in aqueous solutions are complex phenomena that govern many important chemical and biological processes. For example, the intermolecular interactions of proteins dictate their spatio-temporal distributions, such as cluster formation, aggregation and liquid-liquid phase separation. Although the percentage of non-polar residues on protein surfaces may be as high as 70%, the cellular concentrations of proteins are maintained at extremely high level, i.e. up to 40% in volume fraction. In comparison, most synthetic colloidal systems precipitate at such high concentrations due to various attractive interactions and electrolyte screening of Coulomb repulsion. One of the most important forces in water-based chemical and biological environments is the hydrophobic interaction as displayed in lipid bilayer organisation and protein folding. Although vital at the bionano interface, its underlying principles have not been fully understood. In our group, we have developed a modular platform, which is based on the synthesis of gold nanoparticles with a labile capping agent followed by subsequent functionalization with prescribed mixtures of target thiol ligands. This approach not only caters for tailored nanoscale colloids with tunable ligand shells but also offers the investigation of colloidal phenomena by small angle X-ray scattering (SAXS) due to the pronounced scattering length density of the Au core. The obtained scattering profiles can then be used to extract colloidal interaction terms via machine learning algorithms (carried out in collaboration). Based on some preliminary work (and in combination with complimentary techniques), this model system offers unique opportunities to unravel colloidal phenomena found in nature with relevance for fundamental science but also various industrial applications (e.g. in drug delivery, biosensing, food science and personal care).The project will build on these preliminary studies to establish an integrated synthetic and analytical approach to mimic colloidal interactions found in nature and unravel their unusual properties. To this end, the work will be carried out in 4 stages: Stage 1. Platform development (Month 1-12). The first year until the viva upgrade will be dedicated to platform development, i.e. - synthesis of suitable gold nanoparticles with low dispersity, tunable core size and adaptable ligand shell- investigation of colloidal stability by SAXS- implementation of machine learning algorithms to interpret SAXS data with advanced models (extended DLVO theory)Training will be critically important, with extended stays envisioned with collaborators (data science: Dr Keith Butler, QMUL; SAXS: Prof Stefan Förster) as well as participation in summer / winter schools to engage with the community. This phase will completed with the drafting and defense of the upgrade viva. Stage 2. Unravelling protein solubility (Month 13-24).Knowledge acquired in stage 1 will serve to create accurate mimics of natural proteins by matching of size and ligand composition. Amphiphilic molecules will serve as hydroptropes in order to study critical factors for colloidal stability and implement these for novel records of gold nanoparticle solubility. Findings will serve for collaborations with computational colleagues, such as Dr Seishi Shimidzu from the University of York. Stage 3. Triggered molecular recognition phenomena (Month 25-36). The final experimental stage of the PhD is currently envisioned to be used for the study of molecular recognition in native environments. The experimental tool-kit developed herein will be complemented by studies of interfacial adsorption phenomena using quartz crystal microbalance with dissipation monitoring. Synergies are expected with other PhD studies in my group, e.g. on automation and high throughput characterisation.