Interactions between Membranes and "metaphilic" Polypeptide Architectures with Diverse Side-Chain Populations

Michelle W. Lee, Ming Han, Guilherme Volpe Bossa, Carly Snell, Ziyuan Song, Haoyu Tang, Lichen Yin, Jianjun Cheng, Sylvio May, Erik Luijten, Gerard C.L. Wong*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

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 × 108 Pa), 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.

Original languageEnglish (US)
Pages (from-to)2858-2871
Number of pages14
JournalACS nano
Volume11
Issue number3
DOIs
StatePublished - Mar 28 2017

Keywords

  • amphiphilic
  • antimicrobial peptides
  • cell-penetrating peptides
  • membranes
  • peptide membrane interactions

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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    Lee, M. W., Han, M., Bossa, G. V., Snell, C., Song, Z., Tang, H., Yin, L., Cheng, J., May, S., Luijten, E., & Wong, G. C. L. (2017). Interactions between Membranes and "metaphilic" Polypeptide Architectures with Diverse Side-Chain Populations. ACS nano, 11(3), 2858-2871. https://doi.org/10.1021/acsnano.6b07981