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

Sergio Acosta, Zhou Ye, Conrado Aparicio, Matilde Alonso, José Carlos Rodríguez-Cabello

Research output: Contribution to journalArticlepeer-review

Abstract

Antimicrobial peptides (AMPs) have attracted great interest as they constitute one of the most promising alternatives against drug-resistant infections. Their amphipathic nature not only provides them antimicrobial and immunomodulatory properties but also the ability to self-assemble into supramolecular nanostructures. Here, we propose their use as self-assembling 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.

Original languageEnglish (US)
Pages (from-to)4043-4052
Number of pages10
JournalBiomacromolecules
Volume21
Issue number10
DOIs
StatePublished - Oct 12 2020

Bibliographical note

Funding Information:
Authors would like to acknowledge the use of “Servicio General de Apoyo a la Investigación-SAI”, University of Zaragoza (Spain). Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. The authors are grateful for the funding from the Spanish Government (MAT2016-78903-R and RTI2018-096320-B-C22), Junta de Castilla y León (VA317P18), Interreg V A España Portugal POCTEP (0624_2IQBIONEURO_6_E), and Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León. This research was also supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number R01DE026117 to C.A.] and the National Institutes of Health’s National Center for Advancing Translational Sciences [Translational Research Development Program-TRDP award to Z.Y. from grant UL1TR002494]. The funding bodies had no role in study design, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
Copyright © 2020 American Chemical Society.

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