Coupling Phase Behavior of Fatty Acid Containing Membranes to Membrane Bio-Mechanics

Abstract

Biological membranes constantly modulate their fluidity for proper functioning of the cell. Modulation of membrane properties via regulation of fatty acid composition has gained a renewed interest owing to its relevance in endocytosis, endoplasmic reticulum membrane homeostasis, and adaptation mechanisms in the deep sea. Endowed with significant degrees of freedom, the presence of free fatty acids can alter the curvature of membranes which in turn can alter the response of curvature sensing proteins, thus defining adaptive ways to reconfigure membranes. Most significantly, recent experiments demonstrated that polyunsaturated lipids facilitate membrane bending and fission by endocytic proteins – the first step in the biogenesis of synaptic vesicles. Despite the vital roles of fatty acids, a systematic study relating the interactions between fatty acids and membrane and the consequent effect on the bio-mechanics of membranes under the influence of fatty acids has been sparse. Of specific interest is the vast disparity in the properties of cis and trans fatty acids, that only differ in the orientation of the double bond and yet have entirely unique and opposing chemical properties. Here we demonstrate a combined X-ray diffraction and membrane fluctuation analysis method to couple the structural properties to the biophysical properties of fatty acid-laden membranes to address current gaps in our understanding. By systematically doping pure dioleoyl phosphatidylcholine (DOPC) membranes with cis fatty acid and trans fatty acid we demonstrate that the presence of fatty acids doesn’t always fluidize the membrane. Rather, an intricate balance between the curvature, molecular interactions, as well as the amount of specific fatty acid dictates the fluidity of membranes. Lower concentrations are dominated by the nature of interactions between the phospholipid and the fatty acids. Trans fatty acid increases the rigidity while decreasing the area per lipid similar to the properties depicted by the addition of saturated fatty acids to lipidic membranes. Cis fatty acid however displays the accepted view of having a fluidizing effect at small concentrations. At higher concentrations curvature frustration dominates, leading to increased rigidity irrespective of the type of fatty acid. These results are consistent with theoretical predictions as detailed in the manuscript.

EPA and DHA differentially modulate membrane elasticity in the presence of cholesterol

“…We found that EPA and DHA similarly increase k c compared to OA and membranes without any FFAs (Table 3). This increase in bending stiffness in the presence of fatty acids is consistent with previous studies on model membranes, in which FFAs alter the area per lipid of membrane amphiphiles and the resulting curvature strain increases k c (45). In addition, our observation of no significant difference between the bending stiffness of EPA-versus DHA-containing membranes is consistent with atomic force microscopy measurements of cells enriched in EPA and DHA (19), though these studies observed a decrease in bending stiffness upon EPA and DHA addition.…”

Membrane Vesicle Production as a Bacterial Defense Against Stress

“…An increased trans/cis ratio results in a more rigid membrane ( Diefenbach et al, 1992 ; Chen et al, 1995 ). Indeed, under non-stressed conditions, unsaturated fatty acids exhibit a cis configuration, and the double bond present displays an unmovable bend of 30° ( Tyler et al, 2019 ). This kink leads to steric hindrance within the fatty acid residues, thereby enhancing membrane fluidity.…”

Self-consistent field modeling of mesomorphic phase changes of monoolein and phospholipids in response to additives

“…phospholipid) bilayers, yet on an experimental level almost all data concern long-chain fatty acids like oleic acids. 61,62 From these, we only found one (very recent) article on fatty acid containing bilayers in the context of phase behaviour. 61 It reported that the long chain fatty acids used, oleic acid (OA) and elaidic acid (EA), increased the mean bending rigidity of a DOPC bilayer.…”