title: Protein microgels from amyloid fibril networks.
abstract: Nanofibrillar forms of proteins were initially recognized in the context of pathology, but more recently have been discovered in a range of functional roles in nature, including as active catalytic scaffolds and bacterial coatings. Here we show that protein nanofibrils can be used to form the basis of monodisperse microgels and gel shells composed of naturally occurring proteins. We explore the potential of these protein microgels to act as drug carrier agents, and demonstrate the controlled release of four different encapsulated drug-like small molecules, as well as the component proteins themselves. Furthermore, we show that protein nanofibril self-assembly can continue after the initial formation of the microgel particles, and that this process results in active materials with network densities that can be modulated in situ. We demonstrate that these materials are nontoxic to human cells and that they can be used to enhance the efficacy of antibiotics relative to delivery in homogeneous solution. Because of the biocompatibility and biodegradability of natural proteins used in the fabrication of the microgels, as well as their ability to control the release of small molecules and biopolymers, protein nanofibril microgels represent a promising class of functional artificial multiscale materials generated from natural building blocks.
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, U.K.
authors.forename: Ulyana
authors.initials: U
authors.lastname: Shimanovich
authors.forename: Igor
authors.initials: I
authors.lastname: Efimov
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Mason
authors.forename: Patrick
authors.initials: P
authors.lastname: Flagmeier
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Buell
authors.forename: Aharon
authors.initials: A
authors.lastname: Gedanken
authors.forename: Sara
authors.initials: S
authors.lastname: Linse
authors.forename: Karin S
authors.initials: KS
authors.lastname: Åkerfeldt
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: David A
authors.initials: DA
authors.lastname: Weitz
authors.forename: Tuomas P J
authors.initials: TP
authors.lastname: Knowles
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D004355:Drug Stability; D005782:Gels; D006801:Humans; D009113:Muramidase / Q000737:chemistry* / Q000633:toxicity; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D004337:Drug Carriers; D005782:Gels; D009113:Muramidase
keywords: drug release; lysozyme; microfluidics; microgels; protein nanofibrils