title: Sticky water surfaces: helix-coil transitions suppressed in a cell-penetrating peptide at the air-water interface.
abstract: GALA is a 30 amino acid synthetic peptide consisting of a Glu-Ala-Leu-Ala repeat and is known to undergo a reversible structural transition from a disordered to an α-helical structure when changing the pH from basic to acidic values. In its helical state GALA can insert into and disintegrate lipid membranes. This effect has generated much interest in GALA as a candidate for pH triggered, targeted drug delivery. GALA also serves as a well-defined model system to understand cell penetration mechanisms and protein folding triggered by external stimuli. Structural transitions of GALA in solution have been studied extensively. However, cell penetration is an interfacial effect and potential biomedical applications of GALA would involve a variety of surfaces, e.g., nanoparticles, lipid membranes, tubing, and liquid-gas interfaces. Despite the apparent importance of interfaces in the functioning of GALA, the effect of surfaces on the reversible folding of GALA has not yet been studied. Here, we use sum frequency generation vibrational spectroscopy (SFG) to probe the structural response of GALA at the air-water interface and IR spectroscopy to follow GALA folding in bulk solution. We combine the SFG data with molecular dynamics simulations to obtain a molecular-level picture of the interaction of GALA with the air-water interface. Surprisingly, while the fully reversible structural transition was observed in solution, at the water-air interface, a large fraction of the GALA population remained helical at high pH. This "stickiness" of the air-water interface can be explained by the stabilizing interactions of hydrophobic leucine and alanine side chains with the water surface.
authors.affiliation: Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Schach
authors.affiliation: Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Globisch
authors.affiliation: Van't Hoff Institute for Molecular Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Roeters
authors.affiliation: Van't Hoff Institute for Molecular Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Woutersen
authors.affiliation: Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Fuchs
authors.affiliation: Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
authors.forename: Clemens K
authors.initials: CK
authors.lastname: Weiss
authors.affiliation: Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
authors.forename: Ellen H G
authors.initials: EH
authors.lastname: Backus
authors.affiliation: Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
authors.affiliation: Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
authors.forename: Mischa
authors.initials: M
authors.lastname: Bonn
authors.affiliation: Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Peter
authors.affiliation: Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weidner
mesh_terms: D000388:Air / Q000032:analysis; D000595:Amino Acid Sequence; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013499:Surface Properties; D014867:Water / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D010455:Peptides; D014867:Water; C066951:GALA peptide