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

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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).