Studying biological membrane stability

A biophysical thesis at Physical Chemistry and Soft Matter (PCC), as part of a BSc/MSc Molecular Life Sciences or Biotechnology

Background

Biological membranes are of utmost importance in cell life as they play a central role in the structure and function of all cells. First and foremost membranes define boundaries, both between the cell and its surroundings as intracellular. In addition to being a boundary, the cell membrane plays a key role in transport, recognition and communication. These processes can occur by actual passage of ions or molecules across the membrane but also information can be transmitted by conformational changes induced in membrane components. In addition, many metabolic transformations, for example the respiratory chain (including ATP synthesis) are performed by membrane-bound enzyme systems.

As membranes play such a fundamental role in many cellular processes, the composition of the membrane is very complex. It consists of a wide variety of biomolecules, notably lipids and proteins (see figure 1). Studying biological processes associated with a membrane is quite hard as controlling all parameters and components is extremely difficult, if not impossible. Therefore, simplified yet sufficiently detailed model systems are necessary to investigate and quantify these processes. Such models come either in the form of lipids vesicles (liposomes) or planar lipid bilayers (see figure 2). Nowadays, the supported lipid bilayer (SLB) is widely used to investigate membrane properties as it has some unique advantages. Apart from the high stability, their flat geometry makes these membranes eligible to various surface techniques like atomic force microscopy (AFM), reflectometry and total internal reflection fluorescence (TIRF) microscopy among others. Furthermore, it is possible to generate asymmetric lipid bilayers where one leaflet has a different composition than the other leaflet.

Figure 1: A Schematic representation of a lipid vesicle (liposome) and a flat lipid membrane
Figure 1: A Schematic representation of a lipid vesicle (liposome) and a flat lipid membrane

Our Project

We are interested in the stability of biological membranes especially during interactions with biomolecules like antibiotics or antimicrobial peptides (AMPs). For our studies we aspire to create double bilayer systems supported on peptidoglycan to mimic gram-negative bacterial cell membranes.

A thesis in this project can focus on multiple aspects in this project.

For example, a project can focus on creating asymmetric bilayers. In particular, creating asymmetric bilayers due to lipid exchange after the SLB has been formed is something we are very interested in.

Another focus of your thesis project could be on forming double membranes. Some preliminary data on using telechelics as linkers between these membranes shows a lot of promise and we would definitely appreciate it if someone would continue with this project.

Ultimately we are interested in the stability of the membrane and what happens once we let biomolecules interact with it. A thesis project therefore could focus on performing multiple experiments on the interaction of a biomolecule with the membrane.

Figure 2: A Schematic representation of a biomembrane consisting of multiple components like phospholipids, cholesterol, proteins and more.   [Encyclopaedia Brittanica. Membrane (biology). 2008. url: https:// www.britannica.com/science/membrane-biology]
Figure 2: A Schematic representation of a biomembrane consisting of multiple components like phospholipids, cholesterol, proteins and more. [Encyclopaedia Brittanica. Membrane (biology). 2008. url: https:// www.britannica.com/science/membrane-biology]

During these theses you will gain understanding of the physical properties of a lipid membrane, learn how to set up experiments and use different relevant techniques like AFM, TIRF microscopy and reflectometry. Your contribution to our biomembrane activities will be highly appreciated!