Master Student Project – Molecular dynamics (MD) simulation on polymeric vesicle architecture
(Joint MSc project between Group Theory of Polymers and Soft Matter, Applied Physics and Bio-Organic Chemistry Group, Chemical Engineering and Chemistry)
Interest in fundamental research on the formation of polymeric vesicles
No MD simulation experience required
Polymersomes are an interesting group of polymeric (micro/nano) vesicles. These vesicles are formed due to the self-assembly of amphiphilic block copolymers into a well-defined nano/micro structure (100- 500 nm). Due to their ability to encapsulate cargo, e.g. antigen/peptides, it is possible to use polymersomes for drug delivery systems. By altering the composition of the block copolymer it is possible to control the polymersome size, membrane thickness and shape. For biological systems (uptake, cell response, etc.) the morphology (size, shape, membrane thickness) of these polymersomes is highly important and, consequently, we are interested in controlling these parameters. Traditionally, the morphology of assemblies of low molecular weight amphiphiles is predicted by using the packaging parameter p=v/(a0*lc) where v = volume of the hydrophobic chain, a0 = area of the hydrophilic head and lc = length of the hydrophobic chain. Generally vesicles are formed when 1/2 ≤ p ≤ 1.
However, in case of polymeric amphiphiles the packaging parameter is too limited. Besides interactions of the copolymer with itself, neighboring copolymers and its environment, i.e. solvent and non-solvent, the folding of the polymer is an extremely important factor and is difficult to predict without modeling.
The goal of this master project is to use computer simulations to calculate the folding of the used block copolymers and its interactions, to correlate its composition to the morphology. Also, some of the formed polymersomes have semi-permeable membranes. By simulating membrane density this behavior can be explained and predicted. Another feature closely related to this permeability is the ability of the polymersome to change its shape by changing the environment (e.g. dialysis against salt). By altering the environment of an already assembled polymersome the change in morphology can be simulated (thanks to the change of interactions of the copolymers with the environment, pressure inside and/or change in membrane density changing the permeability). As we have experimentally access to a wide range of block copolymers, we can effectively validate the model with actual polymer assemblies.
Objectives of the Master student project:
As a Master student you will be given the task to execute MD simulation answering several important research questions. These MD simulations are conducted at an atomistic level giving detailed insight in the interactions of the system. Using these simulations it is possible to explain the behavior of the polymeric vesicles our group fabricates. After simulating these interactions at the atomistic level larger scale coarse grained simulations (DPD) can be done in a more detailed fashion.
Master Student Project - Microfluidic production of giant liposomes
Liposomes are used in as nanoparticles in drug delivery, cell transfection, and membrane models. Due to their similarity to natural cells (both have a phospholipid membrane), they are also used as models of natural cells. These so-called ‘artificial cells” can be loaded with enzymes, substrates, membrane proteins, fluorophores, etc. This versatility makes them ‘engineerable’, which explains their wide-spread use.
There are several established methods to make giant (> 1 um) liposomes, each with their own advantages and drawbacks. In recent years, the fabrication of these giant liposomes using microfluidics has proven to be very interesting due to its high reproducibility and high loading efficiency. For instance, it is possible to load giant liposomes with cell extract and a synthetic plasmid, permitting the production of your protein of interest in a cell-like vesicle. In our group, we want to load liposomes with enzymatic cascades, to create communicating colonies of artificial cells, or to use them to deliver nanoparticles to cells. Microfluidic fabrication of liposomes would greatly help us, since it is reliable, with high efficiency and throughput.
Based on literature reports, the student should design and develop a microfluidic chip to make giant liposomes in a reproducible manner. Different membrane constituents will be used to study the effect on the membrane properties, as well as a variety of loadings to create artificial cells with interesting properties. This project is suitable for students with a wide range of backgrounds, e.g. organic/supramolecular chemistry, but also molecular biology and engineering
Bastiaan Buddingh’, email@example.com, STO 3.33