Biophysical interactions with phospholipid bilayers

The n-3 PUFAs are important components of cell membranes throughout the body, as they are incorporated into the phospholipids that form cell membranes. Each phospholipid molecule is comprised of a headgroup to which fatty acid esters are bound. There are two binding positions, termed 5 -l and sn-l. The acyl chains that bind to these headgroups interact with other chains in neighboring phospholipid molecules within the bilayer, and the level of chain interaction determines the biophysical properties of the membrane. The sn-l position is usually occupied by a saturated fatty acid the sn-2 position is usually occupied by a relatively unsaturated fatty acid chain. 

The first aim of this work was to explore the feasibility of the sunscreen hypothesis, specifically the likelihood that the polyene precursors (44 and 43) to tridachiahydropyrone (9) are located in the phospholipid bilayer of the cell membrane. This was achieved by studying the interactions of the molecules with a series of model membrane systems, utilising fluorescence-based biophysical techniques. 

A key facet of the sunscreen hypothesis involves the location of the biomimetic tridachiahydropyrone precursors, 43 and 44, in the phospholipid bilayer of the cell membrane of the producing mollusc. A range of biophysical studies was thus conducted in order to explore the feasibihty of this sitnation, by assessing the interactions of 43 and 44, along with tridachiahydropyrone (9) itself (Fig. 3.1), with a number of model membrane systems. 

Fluorescence spectroscopy-based biophysical studies of the interactions of 9, 43 and 44 with phospholipid vesicles (PLVs) demonstrated their propensity to bind to membranes, supporting the theory that these compounds are located in the cell membrane of the producing mollusc. The photochemical isomerisation and electrocyclisation reactions of the precursors 43 and 44 to form tridachiahydropyrone (9) were conducted in the PLVs. The racemic nature of the product isolated from these experiments indicates that if the cell membrane is the biological site of this transformation, then any enantioselectivity conferred in the natural system must be due to the presence of other bilayer components, such as integral membrane proteins, not present in the membrane models here used. This raises a limitation of liposomes as models of biological membranes—they are very simplistic versions of a far more complex system (Fig. 5.1). 

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