Ion-dependent nanomechanics and molecular organization in quatsome membranes.

Abstract

Quatsomes (QS) are highly stable unilamellar nanovesicles formed by the self-assembly of quaternary ammonium surfactants and sterols. Despite their growing potential as nanocarriers, the molecular determinants of QS membrane structure and mechanics remain poorly understood, limiting the rational design of optimized formulations. Here, we investigate the effect of surfactant chain length, counterion identity, and solution ionic content on the structural and nanomechanical properties of cholesterol-based QS membranes assembled from alkyltrimethylammonium (CnTA+) salts. Supported bilayers and multilamellar membrane stacks were characterized under varying ionic conditions using atomic force microscopy (AFM), AFM-force spectroscopy, X-ray reflectivity, and molecular dynamics simulations. While surfactant chain length (C14 vs C16) had only minor effects on membrane stiffness and negligible influence on fluidity, counterion identity emerged as the dominant factor governing membrane behavior. Smaller chaotropic tendence, as provided by Cl- compared to Br-, promoted tighter molecular packing, resulting in more compact, stiffer membranes with reduced fluidity and greater resistance to AFM tip penetration, an effect that was further enhanced by increasing the ionic concentration of the surrounding environment. These findings highlight the critical role of ionic composition in regulating QS membrane organization and mechanics, providing a framework for the rational design of QS-based nanomaterials.