Aescin Incorporation and Nanodomain Formation in DMPC Model Membranes

Abstract

The saponin aescin from the horse chestnut tree is a natural surfactant well-known to self-assemble as oriented-aggregates at fluid interfaces. Using model membranes in the form of lipid vesicles and Langmuir monolayers, we study the mixing properties of aescin with the phase-segregating phospholipid 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC). The binary membranes are experimentally studied on different length scales ranging from the lipid headgroup area to the macroscopic scale using small-angle X-ray scattering (SAXS), photon correlation spectroscopy (PCS), and differential scanning calorimetry (DSC) with binary bilayer vesicles and Langmuir tensiometry (LT) with lipid monolayers spread on the surface of aescin solutions. The binary interaction was found to strongly depend on aescin concentration in two well differentiated concentration regimes. Below 7 mol %, the results reveal phase segregation of nanometer-sized aescin-rich domains in an aescin-poor continuous bilayer. Above this concentration, aescin-aescin interactions dominate, which inhibit vesicle formation but lead to the formation of new membrane aggregates of smaller sizes. From LT studies in monolayers, the interaction of aescin with DMPC was shown to be stronger in the condensed phase than in the liquid expanded phase. Furthermore, a destructuring role was revealed for aescin on phospholipid membranes, similar to the fluidizing effect of cholesterol and nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid bilayers.

Aescin-Cholesterol Complexes in DMPC Model Membranes: A DSC and Temperature-Dependent Scattering Study

“…By using this phospholipid, interactions in both the gel and fluid phases are easily experimentally accessible. Moreover, these results can be directly compared to our previous results 25–27 . The methods we employed were small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), wide-angle X-ray scattering (WAXS), and differential scanning calorimetry (DSC).…”

“…1 mol%) the distribution of the steroid can be considered as rather homogeneous in the bilayer 28–30 . The structural analyses were restricted to aescin contents <1 mol% to avoid major structural modifications such as decomposition of the membrane induced by the saponin 25,26 . Hence, at these conditions the aescin-cholesterol interactions are studied while the vesicular character of the samples is still maintained.…”

Self-Assembly of the Bio-Surfactant Aescin in Solution: A Small-Angle X-ray Scattering and Fluorescence Study

“…Effects directly related to the interaction of aescin with the membranes of the cells contained in the veins have not been mentioned in this context so far. Nevertheless, it is known that aescin interacts with lipid membranes [18,[39][40][41], but the physico-chemical interaction on the molecular scale is still not fully understood. However, the behavior of aescin in solution, especially above the cmc, is essential to elucidate the structure-activity relationship with lipid membranes and the mechanism of action of aescin.…”

“…However, the behavior of aescin in solution, especially above the cmc, is essential to elucidate the structure-activity relationship with lipid membranes and the mechanism of action of aescin. [31,41]. Aescin consists of a well-separated polar glyconic part constituted of three sugar molecules and a triterpenic backbone, which represents the aglyconic part.…”

Development and Percutaneous Permeation Study of Escinosomes, Escin-Based Nanovesicles Loaded with Berberine Chloride

“…Between 1 and 6-7 mol % of ESN, the formation of vesicles was also observed, but large aggregates that precipitate over time occurred. Micelle-sized structures were formed at ESN contents above 6-7 mol % [16].…”