title: Thermally induced conformational transitions in nascent branched amphiphilic peptide capsules.
abstract: Branched amphiphilic peptide capsules (BAPCs) are biocompatible, bilayer delimited polycationic nanospheres that spontaneously form at room temperature through the coassembly of two amphiphilic branched peptides: bis(FLIVI)-K-K4 and bis(FLIVIGSII)-K-K4. BAPCs are readily taken up by cells in culture, where they escape and/or evade the endocytic pathway and accumulate in the perinuclear region, persisting there without apparent degradation or extravasation. Drugs, small proteins, and solutes as well as α particle emitting radionuclides are stably encapsulated for extended periods of time. BAPC formation at room temperature proceeds via a fusogenic process and after 48 h a range of BAPCs sizes are observed, from 50 nm to a few microns in diameter. It was previously reported that cooling BAPCs from 25 to 4 °C and then back to 25 °C eliminated their fusogenic property. In this report, biophysical techniques reveal that BAPCs undergo thermosensitive conformational transitions as a function of both time and temperature and that the properties of BAPCs vary based on the temperature of assembly. The solvent dissociation properties of BAPCs were studied as well as the contributions of specific amino acid residues to the observed conformations. The roles of the potential stabilizing forces present within the bilayer that bestow the unusal stability of the BAPCs are discussed. Ultimately this study presents revised assembly protocols for preparing BAPCs with discrete sizes and solvent-induced extravasation properties.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66502, United States.
authors.forename: Pinakin
authors.initials: P
authors.lastname: Sukthankar
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66502, United States.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Whitaker
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66502, United States.
authors.forename: Macy
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66502, United States.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Herrera
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66502, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Boatwright
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66502, United States.
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas 66502, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Tomich
mesh_terms: D000595:Amino Acid Sequence; D002214:Capsules; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D055550:Protein Stability; D013696:Temperature; D013997:Time Factors
chemical_list: D002214:Capsules; D010455:Peptides