Molecular architectures of self-assembling peptides for combating resistant bacteria

The rapid escalation of antimicrobial resistance has intensified the search for alternative strategies beyond conventional antibiotics. Self-assembling peptides (SAPs) have emerged as a versatile class of antimicrobial materials, capable of forming supramolecular architectures that interact with bacterial membranes, biofilms, and host environments. Rather than acting solely as molecular antimicrobials, SAPs derive their function from architecture-dependent properties, including morphology, charge distribution, and dynamic assembly state. This review critically examines recent advances in SAP design for combating resistant bacteria, with emphasis on the relationship between peptide structure, supramolecular organization, and antibacterial function. We discuss how distinct assemblies modulate membrane disruption, biofilm penetration, intracellular targeting, and antibiotic synergy, while also addressing key translational challenges such as stability, cytotoxicity, and scalability. This review integrates structural principles with biological outcomes to establish a framework in which SAPs are understood as adaptable antimicrobial platforms rather than direct substitutes for traditional antibiotics.