Modulation of the lipid membrane’s tension response by cis-trans isomerism of incorporated fatty acids

Certain fatty acid isomers have been linked to the development of several pathological conditions. For example, while oleic acid – a monounsaturated, cis fatty acid – is considered part of a healthy diet, its trans analogue elaidic acid is associated with an increased risk of developing cardiovascular diseases. Fatty acids can insert into cellular lipid membranes, changing their structural and biophysical features, and these alterations are believed to underpin some of the biomedical effects of these molecules. In this work, we unveil the effect of oleic and elaidic acid on the structure, lateral organization, and microviscosity of model membranes by using a combination of X-ray scattering and viscosity-sensitive dyes (‘molecular rotors’). Our results suggest that the cis isomer, oleic acid, is a more effective lineactant and minimizes the height mismatch between different lipid phases while maintaining the membrane’s lateral heterogeneity. We demonstrate that, as a consequence, the presence of oleic acid successfully dampens changes in membrane microviscosity under tension.