Membrane-perturbing effect of fatty acids and lysolipids

Due to their amphipathicity fatty acids and lysolipids incorporate into lipid membranes and may hence exert an effect on membrane permeability, morphology, and stability. Several studies have shown that fatty acids and lysolipids can reduce the permeability barrier of model membranes. The origin of this phenomenon may be related to changes in the curvature stress of the membrane caused by the effective non-cylindrical geometry of fatty acids and lysolipids. Therefore, it has been proposed that the same effects may carry over to apply to the permeability barrier of cell membranes, in which case the effect could possibly be exploited to enhance intracellular drug uptake. However, fatty acids and lysolipids are in themselves cytotoxic in micromolar concentrations. Experiments with living cells have shown that fatty acids and lysolipids at concentrations below their cytotoxicity limit cannot render cell membranes more permeable by perturbing the lipid bilayer component of the membrane. We summarize the limited, though, conclusive, available literature on this topic. The picture that emerges from this discussion illustrates the importance of a lipidology-based view for the rational development of liposomal drug-delivery systems. It is also an example of possible limitations in translating knowledge from simple lipid bilayers to real biological membranes.