Lipid bilayer stability in relation to oxide nanoparticles

Lipid bilayer stability in relation to oxide nanoparticles

All living organisms are composed of cells that are filled with a thick molecular soup. These molecules constitute a complex machinery that brings these cells to life. To contain these molecules, and to protect them from the hostile outer environment, a phospholipid bilayer envelopes the cell. It is essential that this lipid bilayer, also known as the cell membrane, should remain intact and form a perfect barrier at all times. Industrially manufactured nanoparticles are suspect to be able to penetrate this barrier, and thus endanger living organisms in the environment. This thesis deals with some aspects of the structural integrity of lipid bilayers, and especially how this integrity is affected by the interaction with nanoparticles.

Experiments were performed with silica and titanium dioxide nanoparticles, interacting with lipid bilayers, using a variety of experimental techniques. In addition, a theoretical model was applied that is based on the Scheutjens-Fleer Self Consistent Field (SCF) theory. This model delivered detailed  structural and thermodynamic information about the lipid bilayer. The modelling work helped us to improve our understanding of lipid bilayer stability, and showed the effect of the interaction with the nanoparticles on the phospholipid bilayer. These latter results could be related directly to our experiments.

Let us first experimentally regard the interaction of lipid bilayers with synthetic oxide nanoparticles. We developed a protocol for high-throughput screening of the nanoparticle-bilayer interaction using a fluorescence technique. Results from this method were combined with reflectometry measurements and atomic force microscopy (AFM). The combination of these methods allowed us to relate lipid bilayer integrity to its interaction with nanoparticles and their adsorption onto the bilayer. In addition, the AFM results yielded detailed structural information at the nano-scale. We found that the interaction strongly depends on both lipid bilayer and nanoparticle charge. However, the specific interaction that depends on the nanoparticle type, starts to play a role when the charges are low. When the total interaction strength is regarded, a regime was found at which interaction is strong enough for the nanoparticles to adsorb onto the bilayer, but too weak to disrupt the bilayer. If, however, the bilayer is disrupted by the nanoparticles, the particle may steal away some lipid molecules from the bilayer, and leave again to disrupt the bilayer elsewhere.

Let us now go into more detail on the SCF modelling. Bilayers are composed of phospholipids, which consist of a hydrophilic head group, and a hydrophobic tail. These bilayers were modelled using a single lipid molecule type, of which the head group structure and lipid tail length could be varied. We thus obtained bilayers that varied in their thickness, and the space that a single lipid takes within the bilayer. Changes in bilayer composition affect the bilayer mechanical properties, such as those constants that describe bilayer stretching or bending. This thesis shows how vesicles, which are bilayers in a globular shape, may become unstable if the bilayer lipid composition is changed. Under certain conditions, a vesicle would prefer to fall apart into many smaller vesicles, which is when highly charged head groups start to repel each other. Or the bilayer may form continuous cubic phases, which might occur if lipids with uncharged head groups but with very long tails are used to form the bilayer. Under very specific and finely tuned conditions, a lipid bilayer may become unstable to form stable pores in the membrane, or to fall apart into tiny lipid discs.