Molecular Mechanism of Polyphosphate-Mediated Nanosheet Self-Assembly

Polyphosphate (polyP), a biocompatible and biodegradable polymer, holds significant promise for drug delivery applications. Recent studies reveal that polyP and Mn²⁺ ions can self-assemble into nanosheets, with cetrimonium (CTA) acting as a templating agent. However, the underlying molecular mechanism remains poorly understood. Using coarse-grained molecular dynamics simulations, we reveal that polyP and CTA form a stable, sandwich-like nanostructure, with polyP positioned at the center. Self-assembly is driven by hydrophobic interactions, with curvature controlled by surface tension, which is determined by the interplay of electrostatic and hydrophobic interactions at the polyP/CTA interface. The addition of Mn²⁺ and oleate ions into the solution flattens the structure, while higher polyP-to-CTA ratios promote Mn²⁺ penetration. These findings highlight the power of simulations in uncovering self-assembly mechanisms and advancing applications in drug delivery.