Molecular Crystallization Controlled by pH Regulates Mesoscopic Membrane Morphology

Abstract

Coassembled molecular structures are known to exhibit a large variety of geometries and morphologies. A grand challenge of self-assembly design is to find techniques to control the crystal symmetries and overall morphologies of multicomponent systems. By mixing +3 and -1 ionic amphiphiles, we assemble crystalline ionic bilayers in a large variety of geometries that resemble polyhedral cellular crystalline shells and archaea wall envelopes. We combine TEM with SAXS and WAXS to characterize the coassembled structures from the mesoscopic to nanometer scale. The degree of ionization of the amphiphiles and their intermolecular electrostatic interactions are controlled by varying pH. At low and high pH values, we observe closed, faceted vesicles with two-dimensional hexagonal molecular arrangements, and at intermediate pH, we observe ribbons with rectangular-C packing. Furthermore, as pH increases, we observe interdigitation of the bilayer leaflets. Accurate atomistic molecular dynamics simulations explain the pH-dependent bilayer thickness changes and also reveal bilayers of hexagonally packed tails at low pH, where only a small fraction of anionic headgroups is charged. Coarse-grained simulations show that the mesoscale geometries at low pH are faceted vesicles where liquid-like edges separate flat crystalline domains. Our simulations indicate that the curved-to-polyhedral shape transition can be controlled by tuning the tail density in regions where sharp bends can form the polyhedral edges. In particular, the pH acts to control the overall morphology of the ionic bilayers by changing the local crystalline order of the amphiphile tails.

Faceted phospholipid vesicles tailored for the delivery of Santolina insularis essential oil to the skin

“…Therefore, our results have to be regarded as a first approximation. In previous findings, the faceting of otherwise smooth, rounded vesicles, seemed to occur when the lipids constituting the bilayer were below the gel (L β ) to fluid (L α ) transition temperature [34][35][36][37] and to be produced by the induction of asymmetry in rigid bilayer domains with ordering in the plane of the bilayer [38]. From the analysis of the WAXS domains of our formulations, the presence of a weak peak at around 1.52 Å -1 was noticed, which coincides with the peak attributed to L β or L β' ( Figure 2E, F) [39].…”

Responsive self-assemblies based on fatty acids

“…Recently, studies from Olvera de la Cruz's research group have highlighted how both the selfassembled structures at the mesoscopic scale and the crystalline order within fatty acid bilayers at the microscopic scale can be easily controlled by pH (by using NaOH) in a catanionic fatty acid system [22,38,39]. They studied palmitic acid in the presence of a cationic component comprising a trivalent cationic headgroup made of three lysine amino acids associated to a hydrophobic palmitoyl tail [39].…”

“…They studied palmitic acid in the presence of a cationic component comprising a trivalent cationic headgroup made of three lysine amino acids associated to a hydrophobic palmitoyl tail [39]. The key parameter in this catanionic system is the headgroups stoichiometric ratio.…”

Predicting proton titration in cationic micelle and bilayer environments

“…In another example, knowledge of the protonation state of antiinflammatory drugs is highly desirable, as it affects the partitioning within and transport through the cell membranes, potentially hindering efficacy or causing unwanted side effects. 6 Molecular dynamics (MD) simulations have been applied in the past to examine the effect of protonation state on the structure and dynamics of surfactant or lipid bilayers, [6][7][8][9] micelles, 9 and vesicles. 10 However, these simulations were performed with fixed protonation states, and as such they cannot give pK a 's or model pH-dependent conformational changes or phase transitions.…”