The effect of cationic gemini surfactants upon lipid membranes. An experimental and molecular dynamics simulation study

Abstract

Gemini surfactants possess interesting interfacial and aggregation properties that have prompted comprehensive studies and successful applications in a wide variety of fields. However, a systematic study on the effect of gemini tail and spacer length upon the organization of lipid membranes has not been presented so far. In this study, we analyze the action of dicationic alkylammonium bromide gemini surfactants on DPPC liposomes, the latter employed as a model of lipid membranes. Differential scanning calorimetry results indicate that the surfactants presenting shorter tails (12 carbons) induce a decrease in the overall order of the bilayer, while those with longer tails (16 and 18 carbons) lead to the formation of more ordered structures. The respective influence on the degree of lipid order transverse to the bilayer was additionally studied resorting to a detailed fluorescence anisotropy study. In this case, it is observed that among the shorter tail surfactants, those with longer spacers (6 and 10 carbons) are responsible for a more pronounced disrupting effect upon the membrane, especially close to the lipid polar heads. Molecular dynamics simulation supports the most important findings and provides insight into the mechanism that governs this interaction. Accordingly, the interplay between tail and spacer length accounts for the differential vertical positioning of the gemini molecules and atom-density in the core of the bilayer, that provide a rationale for the experimental observations.

Phospholipid Bilayer-Perturbing Properties Underlying Lysis Induced by pH-Sensitive Cationic Lysine-Based Surfactants in Biomembranes

“…This hypothesis of enhanced incorporation did not lead to increased hemolytic activity or membrane fluidity (see sections 3.1 and 3.2, respectively), possibly because PKM may increase the packing degree of the lipid bilayer and thus exert a protective effect at sublytic concentrations. 5 Finally, as we have demonstrated no noticeable change in the membrane proteins' profile after surfactant treatments at physiological pH, the surfactant-protein interaction might not be involved in the morphological changes undergone by the erythrocytes in this condition. Our findings contradict studies of some authors 35,57 that reported the proteins of the membrane skeleton and integral membrane proteins as responsible for the shape of erythrocytes.…”

“…[2][3][4][5][6] Surfactants derived from amino acids constitute an important class of natural surface-active biomolecules that usually have biocompatible properties and multifunctional capabilities, which make them extremely relevant for pharmaceutical applications, especially in the field of novel non-viral drug delivery devices. 4,7,8 Our group has considerable experience in the synthesis of surfactants derived from amino acids.…”

Dicationic Alkylammonium Bromide Gemini Surfactants. Membrane Perturbation and Skin Irritation

“…Those of positive charge are typically more effective as permeation enhancers than the alternative anionic and nonionic compounds, although cytotoxicity is potentially more significant in cationic systems [4], [5]. Among several classes of surface-active compounds, dicationic alkylammonium bromide gemini surfactants were chosen, since they are known to efficiently modulate the order in biomembranes as indicated in a previous publication by some of the authors [6].…”

A Study of the Interaction between a Family of Gemini Amphiphilic Pseudopeptides and Model Monomolecular Film Membranes Formed with a Cardiolipin

“…20 Furthermore, gemini surfactants have been proposed as active antibacterial agents. 21 The C2-symmetry GAPs considered in this work ( Figure 1) have interesting self-assembling properties. Indeed, these tailor-made molecules with adjusted properties may be responsive to environmental stimuli like pH.…”