Interactions between DMPC Model Membranes, the Drug Naproxen, and the Saponin β-Aescin

Abstract

In this study, the interplay among the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane, the nonsteroidal anti-inflammatory drug naproxen, and the saponin β-aescin are investigated. The naproxen amount was fixed to 10 mol %, and the saponin amount varies from 0.0 to 1.0 mol%. Both substances are common ingredients in pharmaceutics; therefore, it is important to obtain deeper knowledge of their impact on lipid membranes. The size and properties of the DMPC model membrane upon naproxen and aescin addition were characterized with differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SAXS, WAXS), and photon correlation spectroscopy (PCS) in a temperature-dependent study. The interaction of all substances was dependent on the lipid phase state, which itself depends on the lipid’s main phase transition temperature Tm. The incorporation of naproxen and aescin distorted the lipid membrane structure and lowers Tm. Below Tm, the DMPC–naproxen–aescin mixtures showed a vesicle structure, and the insertion of naproxen and aescin influenced neither the lipid chain–chain correlation distance nor the membrane thickness. Above Tm, the insertion of both molecules instead induced the formation of correlated bilayers and a decrease in the chain–chain correlation distance. The presented data clearly confirm the interaction of naproxen and aescin with DMPC model membranes. Moreover, the incorporation of both additives into the model membranes is evidenced.

The cytoplasmic tail of myelin protein zero induces morphological changes in lipid membranes

“…The sonicated liposomes have a wider span of membrane thickness than bicelles, with a mean thickness of 37.64 Å, when collecting data over several beamtimes (Figure 1B). The mean membrane thickness for the liposomes is larger than reported (Hägerbäumer et al, 2023; Sreij et al, 2018) for pure DMPC liposomes prepared by extrusion. Sonication gives are more variable size of liposomes, and the deviation is expected to be higher than in a more homogenous sample of extruded vesicles; in addition, DMPG will influence the membrane thickness.…”

“…These membrane-mimicking model systems are easily prepared, and different buffers can be applied if necessary. The membrane thickness ( d m,MKP ) was calculated using the MKP method (Hägerbäumer et al, 2023; Sreij et al, 2018) for samples collected at RT from several SAXS beamtimes. Following the calculations from Hägerbäumer et.…”

“…Following the calculations from Hägerbäumer et. al (Hägerbäumer et al, 2023), I(q)× q 4 was plotted against q , before fitting the plots with a fourth-order polynomial (Figure 1A). The SAXS curve of both model systems had the typical broad peak characteristic of a phospholipid bilayer structure.…”

“…The peak position of momentum transfer ( s ) in P0ct-lipid samples was used to calculate repeat distances ( d ) in proteolipid structures using equation 1: Membrane thickness of the protein-free liposomes and bicelles was determined by a modified Kratky-Porod (MKP) analysis. Isq 4 was plotted against s and fitted with a 4 th -order polynomial, and d m,MKP was calculated using equation 2 (Hägerbäumer et al, 2023): …”

“…Figure 1: Characterisation of bicelles and sonicated liposomes. A) Membrane thickness (dm,MKP) was calculated with the MKP method(Hägerbäumer et al, 2023); I(q)×q 4 was plotted against q before fitting the plot with a fourth-order polynomial. The maximal q-value was determined and membrane thickness calculated using equation (2), dm,MKP denoted in the upper right corner.…”