Responding Model Membranes. Lipid Phase Behaviour, Domain Formation and Permeability

Sammanfattning: This thesis concerns the interplay between the lipid phase behaviour, domain formation and the permeability of bilayer membranes. An essential part of this work has been the understanding of the phase transitions and equilibrium properties of lipid bilayers. In this approach experimental results of lipid phase behaviour have been correlated to theoretical descriptions of the systems. An isothermal sorption microcalorimeter was used to study the hydration of phospholipid bilayers. It was found that a decrease in osmotic pressure (water chemical potential) induces a phase transition from gel to liquid crystalline phospholipid bilayers. Phase transitions upon variations in chemical potential were also predicted from the theoretical model based on interlamellar forces and regular solution theory. Phospholipid-cholesterol mixtures at varying osmotic pressures have also been investigated. This study showed on a several unusual features in the phase behaviour, indicating very specific phospholipid-cholesterol interactions. Phase segregation of the lipids involves the formation of differentiated domains in the bilayers. Domain formation in monolayers of fatty acids, ceramides and cholesterol has been investigated by means of AFM. The lipid components were chosen to serve as a model system for the lipids of stratum corneum (the outer layer of human skin). The study showed on large variations of the shape and the size of the domains. In the segregated monolayers, cholesterol acts as a lineactant (analogous to surfactant), reducing the line tension along the domain boundaries. Very small rectangular domains were observed in the ceramide-cholesterol monolayers. These domains were interpreted as two-dimensional single crystals. A theoretical model for describing water and solute transport through a bilayer stack in the presence of a gradient in water chemical potential has been developed. The inspiration for this model is the barrier of stratum corneum. An essential feature of the model is the coupling between the water flux and the thermodynamically response to the water chemical potential. The variation in water chemical potential along the membrane can induce phase transitions and phase segregation. This results in a non-homogenous membrane, where the state of the lipids and the lateral organisation of the segregated domains are crucial for the permeability. The calculated water flux showed qualitative agreement with experimental findings for the water flux through stratum corneum.