Anionic phospholipid variety: a physicochemical study of model mammalian and bacterial cell membranes

Martin, Alexandra L. (2020). Anionic phospholipid variety: a physicochemical study of model mammalian and bacterial cell membranes. University of Birmingham. Ph.D.

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Abstract

Every organism has at least one cell and every cell has a cell membrane that carries out crucial, life-sustaining functions. Whilst membrane proteins are responsible for many of these functions, the lipid bilayer they are embedded in is of great importance to membrane structure and behaviour. These properties are tailored for each cell membrane by its specific lipid composition. Cell membranes are biological interfaces and as such they can be studied using surface science tools. However, their complexity and delicacy make successful cell membrane extraction and characterisation difficult. Therefore, simplified models comprising synthetic phospholipids are frequently used to represent natural cell membranes, such as floating lipid monolayers and supported lipid bilayers.

In the presented work, models of a zwitterionic lipid dimyristoyl phosphatidylethanolamine (DMPE) and its mixtures with anionic lipids dimyristoyl phosphatidylserine (DMPS), dimyristoyl phosphatidylglycerol (DMPG) and tetramyristoyl cardiolipin (TMCL) have been studied. These lipids have been chosen to mimic mammalian cell membrane inner leaflets (DMPE-DMPS mixtures) and bacterial cell membranes (DMPE-DMPG-TMCL mixtures). Their ensemble and structural behaviour have been explored using isotherms, Brewster angle microscopy, electrochemistry, in situ infrared spectroscopy, neutron and x-ray reflectivities and grazing incidence x-ray diffraction.

Results show that greater content of all anionic lipids increases layer solvation which will affect membrane permeability and electrical barrier properties. Different lipid ratios result in varied structure such that low-DMPS content increases lipid packing density whereas the same is observed for greater TMCL content and increasing DMPG levels seems to increase layer fluidity and disorders packing. Deuterium-labelling of lipid tails leads to changes to monolayer organisation, particularly at lower pressures as the monolayers are expanded. These results suggest that at pressures corresponding to the tension of bilayers and cell membranes, deuterated lipid monolayers are less condensed and more fluid than their non-deuterated counterparts. Zwitterionic and anionic lipid monolayer behaviour were both observed to be influenced by the presence of metal cations, although monolayers of greater anionic lipid content were more significantly affected. Sodium and calcium cations both expanded the monolayers and resulted in greater water penetration and sodium ions particularly distorted anionic lipid packing.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):