Dual Self-Assembled Nanostructures from Intrinsically Disordered Protein Polymers with LCST Behavior and Antimicrobial Peptides

Antimicrobial peptides (AMPs) have attracted great interest as they constitute one of the most promising alternatives against drug-resistant infections. Their amphipathic nature provides them antimicrobial and immunomodulatory properties but also the ability to selfassemble into supramolecular nanostructures. Here, we propose their use as selfassembling domains to drive hierarchical organization of intrinsically disordered protein polymers (IDPPs). Using a modular approach, hybrid protein-engineered polymers were recombinantly produced, thus combining designer AMPs and a thermoresponsive IDPP, an elastin-like recombinamer (ELR). We exploited the ability of these AMPs and ELRs to self-assemble to develop supramolecular nanomaterials by way of a dual-assembly process. First, the AMPs trigger the formation of nanofibers, then the thermoresponsiveness of the ELRs enables assembly into fibrillar aggregates. The interplay between the assembly of AMPs and ELRs provides an innovative molecular tool in the development of self-assembling nanosystems with potential use for biotechnological and biomedical applications.Este trabajo forma parte de los proyectos de investigación MAT2016-78903-R y RTI2018-096320-B-C22 del Ministerio de Ciencia e Innovación, del proyecto VA317P18 de la Junta de Castilla y León, del proyecto 0624_2IQBIONEURO_6_E del programa Interreg V A España Portugal POCTEP y del Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y Leó