Structure and Dynamics of Non-Lamellar Lipid Bilayers at Interfaces, Implication in Biomembrane Organisation and Drug Delivery Applications

The Problem

Lipids are the main components of cellular membranes. The main building blocks of the membranes that surround cells are lipid mixtures that form lamellar phases. However, lipids have a rich phase behaviour ranging from micellar, hexagonal or cubic to lamellar and, further, to the reversed counterparts, which are also utilised in many biological systems. The rich phase behaviour in lipids in part explain the complex morphological structures present in certain cellular organelles and also the acute structures produce during membrane invagination and cellular division.

The Challenge

The different lipid phases allow tuning key properties, such as rigidity, curvature and interfacial behaviour which are all essential points for living systems as well as in applications such as drug delivery systems.  Understanding how to selectively manipulate the packing parameter of the building blocks, the ratio of the minimum area of the hydrophilic heads and hydrophobic tails of the lipids or lipid mixtures allows the particular phases can be tuned. This understanding allows us to create smarter drug delivery systems.

The Solution

We have used a combination of grazing incidence neutron spin echo spectroscopy, specular and off-specular neutron reflectivity (NR) and grazing incidence small angle neutron scattering, as well as small angle x-ray scattering to determine the dynamics and structural characteristics of non-lamellar lipid assembly films supported on a silicon block. The results show that we can prepare liquid-crystalline aqueous films of different phases on the surface by changing the lipid composition. The hexagonal phase exhibits oriented domains and the dynamic measurements feature fluctuations in the length and time scales of nanometers and nanoseconds, while the cubic phase suppresses such undulations and show no domain orientation.

The Team

This work results from a tight collaboration between two academic research groups in Lund, Sweden Prof. Tommy Nylander and co-workers, and the Heinz Maier-Leibnitz Zentrum (MLZ), Garching-Munich team in Germany, with Olaf Holderer, Olaf Soldwedel and Henrich Frielinghaus as well as by the drug delivery company CAMURUS, based in Sweden.

See our most recent research paper on the topic

T. Nylander et al., Relationship between Structure and Fluctuations of Lipid Nonlamellar Phases Deposited at the Solid–Liquid Interface; J. Phys. Chem. B 121 (13), 2705 (2017)

Figures 1 and 2: Detector images from neutron reflectometry (NREX) of spin coated layer from mixtures of soy phosphatidylcholine (SPC) and glycerol dioleate (GDO) in excess water (D2O), where images above show data for 35/65 wt%/wt% SPC/GDO (micellar cubic Fd3m) films and the corresponding results for 60/40 wt%/wt% SPC/GDO (reverse hexagonal, HII, phase) are shown below. Both specular (qx=0) and off-specular data are indicated.

Contact

Prof. Tommy Nylander
tommy.nylander@fkem1.lu.se
Physical Chemistry
Lund University