Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile+DPPC mixture

Abstract

The tri-headed anionic dendritic amphiphile, 4-(2-carboxyethyl)-4-[(icosyloxycarbonyl)amino]heptanedioic acid (3CCb20), forms solid-like gel-state mixed micelles with dipalmitoylphosphatidylcholine (DPPC) in excess water at 3CCb20 : DPPC = 0.91 : 1 molar ratio. On heating, these micelles transform into fluid bilayers stacked in the liquid crystalline lamellar L α phase at about 40 °C. This phase transition and the microstructure of 3CCb20 + DPPC aggregates were studied using smalland wide-angle synchrotron X-ray diffraction. The ability of 3CCb20 to solubilize solid-like lipid bilayers could be important in microbiocidal activities of 3CCb20, including in its anti-HIV activity.Keywords: amphiphiles; DPPC; micelles; bilayers; X-ray diffraction; phase transition 3 IntroductionSaturated fatty acids have a long history as microbicides against many pathogens [1][2][3][4][5]. Measurements of inhibitory activities can be problematic because of the very low solubility of saturated fatty acids in aqueous solutions [6]. Furthermore, as the chain length increases to C 18 and beyond, the aqueous solubility becomes immeasurable. Knowing that the compounds completely dissolve in aqueous media enables speculation about how chain length affects microbiological activity. In a homologous series of compounds, antimicrobial activity can show a cut-off effect [7]. Without knowing that the amphiphiles fully dissolve in aqueous media, we cannot conclude that the cut-off effect is due to the "intrinsic" activity of the amphiphiles or due to the decreased solubility of the amphiphile in the microbiological media. The antimicrobial data for 3CCbn show that longer chains (3CCb18-22) are more active than the shorter chains (3CCb14-16). These data contrast with those of saturated fatty acids, where the most active compounds are in the range of C 8 to C 14 [1][2][3][4][5]. A dendritic structure should reduce the absorption of an amphiphile into a cell. The highly branched structure of the head group resembles the dendritic structure of glycolipids that are anchored on the outside of cells. Branching and the triple charge might retard diffusion across membranes. Given the success of very long chain amphiphiles as antimicrobials, there might be a preference for absorption of these amphiphiles on pathogens as opposed to epithelial cells resulting in the reduced irritancy.To understand molecular mechanisms in the biological activities of these compounds, their interactions with different cell constituents must be studied. Several researchers [2,5,19] have proposed that the microbicidal mechanism of action involves fatty acids interacting with membranes. Because of the long alkyl chains, 3CCbn will likely partition into biological membranes. Upon doing so, these amphiphiles will affect the structure and dynamics of the membrane. The phospholipid bilayer comprises the structural matrix of biological membranes. Understanding how amphiphiles interact with a phopholipid bilayer will provide clues to the molecular mechanism of the biological a...

Aescin Incorporation and Nanodomain Formation in DMPC Model Membranes

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