Histidine-substituted β-sheet peptide networks with tunable viscoelasticity and pH-modulated transport.
TL;DR
Three short β-sheet-forming peptides with graded histidine substitution were designed as minimal supramolecular networks to systematically examine how sequence-level variation regulates supramolecular organization, viscoelastic response, and pH-modulated molecular transport in aqueous environments.
Abstract
Peptide-based supramolecular assemblies provide experimentally accessible model systems for probing structure-property relationships in soft molecular materials. Here, three short β-sheet-forming peptides with graded histidine substitution were designed as minimal supramolecular networks to systematically examine how sequence-level variation regulates supramolecular organization, viscoelastic response, and pH-modulated molecular transport in aqueous environments. All peptides spontaneously assembled into β-sheet-rich nanofibrous networks, as confirmed by spectroscopic and microscopic characterization, and exhibited stable viscoelastic behavior with pronounced reversible self-recovery. Using doxorubicin as a representative small-molecule probe, the assemblies displayed distinct pH-dependent transport regimes, and kinetic analysis based on the Korsmeyer-Peppas model revealed sequence- and pH-dependent differences in release behavior. Rather than focusing on detailed molecular-level mechanisms, this work emphasizes experimentally accessible correlations between supramolecular network structure, mechanical response, and transport behavior. These results highlight histidine-substituted β-sheet peptide assemblies as adaptable soft-matter model systems for investigating pH-regulated transport phenomena in supramolecular networks.