title: Noncanonical self-assembly of highly asymmetric genetically encoded polypeptide amphiphiles into cylindrical micelles.
abstract: Elastin-like polypeptides (ELPs) are a class of biopolymers consisting of the pentameric repeat (VPGαG)n based on the sequence of mammalian tropoelastin that display a thermally induced soluble-to-insoluble phase transition in aqueous solution. We have discovered a remarkably simple approach to driving the spontaneous self-assembly of high molecular weight ELPs into nanostructures by genetically fusing a short 1.5 kDa (XGy)z assembly domain to one end of the ELP. Classical theories of self-assembly based on the geometric mass balance of hydrophilic and hydrophobic block copolymers suggest that these highly asymmetric polypeptides should form spherical micelles. Surprisingly, when sufficiently hydrophobic amino acids (X) are presented in a periodic sequence such as (FGG)8 or (YG)8, these highly asymmetric polypeptides self-assemble into cylindrical micelles whose length can be tuned by the sequence of the morphogenic tag. These nanostructures were characterized by light scattering, tunable resistive pulse sensing, fluorescence spectrophotometry, and thermal turbidimetry, as well as by cryogenic transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS). These short assembly domains provide a facile strategy to control the size, shape, and stability of stimuli responsive polypeptide nanostructures.
authors.affiliation: Department of Biomedical Engineering and Research Triangle MRSEC, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: McDaniel
authors.forename: Isaac
authors.initials: I
authors.lastname: Weitzhandler
authors.forename: Sylvain
authors.initials: S
authors.lastname: Prevost
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Vargo
authors.forename: Marie-Sousai
authors.initials: MS
authors.lastname: Appavou
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
authors.forename: Michael
authors.initials: M
authors.lastname: Gradzielski
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000595:Amino Acid Sequence; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004549:Elastin / Q000737:chemistry* / Q000235:genetics; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D044367:Phase Transition; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D001672:Biocompatible Materials; D008823:Micelles; D010455:Peptides; D011994:Recombinant Proteins; D004549:Elastin
keywords: Self-assembly; biomaterials; cryo-TEM; elastin-like polypeptides; protein polymers; small-angle neutron scattering