Thesis subject

MSc - Cell membranes: breaking the barrier using nanoparticles?

Among the most complex systems in science are biological systems. In order to capture this complexity, both physics and chemistry can be applied to bring down any biological system to a level that is possible to tackle.

One of these little understood objects in biology is the plasma membrane. For physicists, this membrane is a mere interface, while for chemists it is a self-assembled structure of an amphiphilic molecule. It is a structure where chemical reactions take place, which protects a cell from its environment, and it creates a boundary to its inner content.

Today, understanding of the phospholipid membrane is crucial in the research on the environmental impact of industrial nanoparticles. These particles are produced and applied in numerous applications, ranging from sunscreens and antibacterial (food) packaging to car-varnish and numerous medical applications. Their risks, however, remain largely unknown, and the particles are suspect to being able to cross the membrane passively. The toxicological studies of these particles have highly increased in number over the last decade, but the fundamental understanding of the particle-membrane interaction remains at a low level. This research, therefore, is targeted to bridge this gap.

As a simple model for biological membranes, lipid vesicles are used: closed phospholipid bilayer membranes. Using pH titrations (which affect the particle charge) in light scattering measurements, we found both shrinking as well as growing vesicle size over the course of the measurements. Fluorescence measurements affirm the dependence of particle charge on the strength of interaction between nanoparticles and phospholipid membranes.

In this project, you will contribute to enhance the understanding of the phospholipid membrane at the level of physical chemistry. As a model system, dioleoyl-phosphatidyl-choline (DOPC) vesicles (figure XX) are used to study the interaction with silica particles ranging from Ø 10 to 500 nm. Confocal microscopy is used to study the direct effect of particles on fluorescently labelled membranes, whereas a fluorescence leakage assay is used to scan the physico-chemical conditions where the particle-membrane interaction is most relevant. Self consistent field (SCF) modelling can be applied to interpret your results at a molecular level.

The chemical structure of dioleoyl-phosphatidyl-choline, the building block of our model-membranes
The chemical structure of dioleoyl-phosphatidyl-choline, the building block of our model-membranes
A cartoon of a phospholipid vesicle. In reality, a vesicle is much larger, and the bilayer much thinner
A cartoon of a phospholipid vesicle. In reality, a vesicle is much larger, and the bilayer much thinner

Experimental techniques:

  • Confocal microscopy
  • Fluorescence spectroscopy.

Other possible techniques:

  • Reflectometry
  • Atomic force microscopy (AFM)
  • Dynamic light scattering (DLS)
  • Self consistent field (SCF) modelling