title: Interactions between Membranes and "Metaphilic" Polypeptide Architectures with Diverse Side-Chain Populations.
abstract: At physiological conditions, most proteins or peptides can fold into relatively stable structures that present on their molecular surfaces specific chemical patterns partially smeared out by thermal fluctuations. These nanoscopically defined patterns of charge, hydrogen bonding, and/or hydrophobicity, along with their elasticity and shape stability (folded proteins have Young's moduli of ∼1 × 108Pa), largely determine and limit the interactions of these molecules, such as molecular recognition and allosteric regulation. In this work, we show that the membrane-permeating activity of antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) can be significantly enhanced using prototypical peptides with "molten" surfaces: metaphilic peptides with quasi-liquid surfaces and adaptable shapes. These metaphilic peptides have a bottlebrush-like architecture consisting of a rigid helical core decorated with mobile side chains that are terminated by cationic or hydrophobic groups. Computer simulations show that these flexible side chains can undergo significant rearrangement in response to different environments, giving rise to adaptable surface chemistry of the peptide. This quality makes it possible to control their hydrophobicity over a broad range while maintaining water solubility, unlike many AMPs and CPPs. Thus, we are able to show how the activity of these peptides is amplified by hydrophobicity and cationic charge, and rationalize these results using a quantitative mean-field theory. Computer simulations show that the shape-changing properties of the peptides and the resultant adaptive presentation of chemistry play a key enabling role in their interactions with membranes.
authors.forename: Michelle W
authors.identifier: 0000-0003-1613-9501
authors.initials: MW
authors.lastname: Lee
authors.forename: Ming
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Physics, North Dakota State University , Fargo, North Dakota 58108, United States.
authors.forename: Guilherme Volpe
authors.initials: GV
authors.lastname: Bossa
authors.affiliation: Department of Physics, North Dakota State University , Fargo, North Dakota 58108, United States.
authors.forename: Carly
authors.initials: C
authors.lastname: Snell
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Lichen
authors.identifier: 0000-0002-4573-0555
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Physics, North Dakota State University , Fargo, North Dakota 58108, United States.
authors.forename: Sylvio
authors.initials: S
authors.lastname: May
authors.forename: Erik
authors.identifier: 0000-0003-2364-1866
authors.initials: E
authors.lastname: Luijten
authors.forename: Gerard C L
authors.initials: GC
authors.lastname: Wong
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D013499:Surface Properties
chemical_list: D023181:Antimicrobial Cationic Peptides; D057846:Cell-Penetrating Peptides
keywords: amphiphilic; antimicrobial peptides; cell-penetrating peptides; membranes; peptide−membrane interactions