Temperature effects on the structural stability of EF K peptide membranes: insights into mono- and multilayer architectures

Abstract

Peptide nanostructures are versatile supramolecular systems with potential applications in biomaterials and nanotechnology, where stability emerges from the cooperative action of noncovalent interactions. In this study, we investigated the bolaamphiphilic peptide EF4K assembled into nanomembranes, focusing on the combined effects of temperature and multilayer organization. Molecular dynamics simulations were conducted at 250, 270, 300, 320, and 350 K in monolayer and multilayer configurations, allowing direct evaluation of peptide−peptide and peptide−solvent interactions. The results demonstrate that while the number of hydrogen bonds increases with temperature, their lifetimes decrease markedly, with reductions of nearly 79%. Peptide−solvent interactions weaken significantly, with losses of up to 90%, whereas multilayer assemblies partially compensate this destabilization by reinforcing peptide−peptide hydrogen bonds and van der Waals contacts. Electrostatic contributions between peptides remain stable and even strengthen in multilayers, indicating supramolecular reinforcement upon stacking. Confined water within multilayers exhibits longer hydrogen bond lifetimes despite a lower number of contacts, contrasting with the destabilization of hydration shells observed in monolayers at higher temperatures. These findings reveal that EF4K membranes undergo a redistribution of stabilizing forces under thermal stress, with multilayers achieving enhanced internal cohesion, thereby highlighting their potential as robust peptide-based nanomaterials.