Journal
ACS NANO
Volume 11, Issue 3, Pages 2858-2871Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.6b07981
Keywords
antimicrobial peptides; cell-penetrating peptides; amphiphilic; membranes; peptide-membrane interactions
Categories
Funding
- National Science Foundation [DMR-1411329, DMR-1610796, DMR-1309525]
- National Institutes of Health [1R21AI117080]
- CAPES Foundation/Brazil Ministry of Education [9466/13-4]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
- DOE Office of Biological and Environmental Research
- National Institutes of Health, National Institute of General Medical Sciences [P41GM103393]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1411329] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1610796, 1309525] Funding Source: National Science Foundation
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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 similar to 1 x 10(8) 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.
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