Theoretical modelling and experimental investigation of polymer-membrane interactions for drug delivery

该博士项目旨在开发有效的计算和理论模型，以理解和预测聚合物与生物膜之间的相互作用，并通过体外实验验证理论预测。研究主题与纳米结构软物质材料及其在药物输送中的应用密切相关，这对医疗保健和福祉至关重要，因此属于EPSRC的职权范围。该项目包括三个紧密相连的并行工作流程，即：(a)计算机模拟和理论建模；(b)生物物理技术；(c)细胞毒性评价。每个流程的结果将指导其他流程的进展。工作计划安排如下：学生将首先接受标准的健康和安全培训，进行文献检索以熟悉研究背景，并接受项目特定建模和实验室技术方面的培训。这项研究将从测试和修改现有的力场开始，以便在全原子水平上模拟聚合物膜系统。将进行生物物理测量以获得初步结果，以验证开发的力场。第二年。原子模拟将用于系统地研究聚合物-膜的相互作用。模拟和实验数据的详细分析将提供相互作用的微观图像，并指导粗粒度MD模拟模型的发展，该模型可以访问比原子模拟更大的时间和长度尺度。年3。将进行粗粒度的MD模拟，以找出控制聚合物-膜相互作用的关键因素。这是通过打开/关闭静电相互作用和调整聚合物结构/链刚度来完成的。最后提出了预测组合体系结构和力学性能的理论模型。模型预测将通过细胞毒性评估进行检验，该评估通过将细胞暴露于一系列聚合物浓度并使用标准技术（例如MTT测定）测量细胞毒性进行。

Title: Theoretical Modelling and Experimental Investigation of Polymer-Membrane Interactions for Drug-DeliveryThis PhD project is aimed at developing efficient computational and theoretical models for understanding and predicting the interactions between polymers and biological membranes and testing the theoretical predictions by in vitro experiments. The research subjects are closely related to nanostructured soft matter materials and their applications in drug delivery which are of essential importance for healthcare and wellbeing and thus fall well in the remit of the EPSRC. This project consists of 3 strongly interlinked working streams which will run in parallel, namely: (a) computer simulations and theoretical modelling; (b) biophysical techniques; (c) cytotoxicity assessment. Results from each stream will guide progression in the others. The work plan is scheduled as follows: Year 1. The student will first undergo standard health and safety training, carry out a literature search to familiarise his or herself with the research background and receive training in project specific modelling and laboratory techniques. The research will start with testing and modifying existing force fields for modelling polymer-membrane systems at the full atomistic level. Biophysical measurements will be performed to obtain preliminary results for validating the developed force fields. Year 2. Atomistic simulations will be carried out to systematically study the polymer-membrane interactions. Detailed analyses of simulation and experimental data will provide a microscopic picture of the interactions and guide the development of coarse-grained MD simulation model that can access much larger time and length scales than atomistic simulations. Year 3. Coarse-grained MD simulations will be performed to find out the key factors that control the polymer-membrane interactions. This is done by switching on/off electrostatic interactions and tuning polymer architectures/chain stiffness. Finally a theoretical model will be proposed for predicting the structural and mechanical properties of the combined systems. Model predictions will be examined by cytotoxicity assessment carried out by exposing the cells to a range of polymer concentrations and measuring cytotoxicity using standard techniques (e.g. MTT assay).