title: Unraveling Hydrophobic Interactions at the Molecular Scale Using Force Spectroscopy and Molecular Dynamics Simulations.
abstract: Interactions between hydrophobic moieties steer ubiquitous processes in aqueous media, including the self-organization of biologic matter. Recent decades have seen tremendous progress in understanding these for macroscopic hydrophobic interfaces. Yet, it is still a challenge to experimentally measure hydrophobic interactions (HIs) at the single-molecule scale and thus to compare with theory. Here, we present a combined experimental-simulation approach to directly measure and quantify the sequence dependence and additivity of HIs in peptide systems at the single-molecule scale. We combine dynamic single-molecule force spectroscopy on model peptides with fully atomistic, both equilibrium and nonequilibrium, molecular dynamics (MD) simulations of the same systems. Specifically, we mutate a flexible (GS)5peptide scaffold with increasing numbers of hydrophobic leucine monomers and measure the peptides' desorption from hydrophobic self-assembled monolayer surfaces. Based on the analysis of nonequilibrium work-trajectories, we measure an interaction free energy that scales linearly with 3.0-3.4 kBT per leucine. In good agreement, simulations indicate a similar trend with 2.1 kBT per leucine, while also providing a detailed molecular view into HIs. This approach potentially provides a roadmap for directly extracting qualitative and quantitative single-molecule interactions at solid/liquid interfaces in a wide range of fields, including interactions at biointerfaces and adhesive interactions in industrial applications.
authors.affiliation: Department for Interface Chemistry and Surface Engineering, Max-Planck-Institut für Eisenforschung GmbH , D-40237 Düsseldorf, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stock
authors.affiliation: Department of Chemical Engineering, University of California Santa Barbara , Santa Barbara, California 93106-5080, United States.
authors.forename: Jacob I
authors.initials: JI
authors.lastname: Monroe
authors.affiliation: Department for Interface Chemistry and Surface Engineering, Max-Planck-Institut für Eisenforschung GmbH , D-40237 Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Utzig
authors.affiliation: Department of Chemical Engineering, University of California Santa Barbara , Santa Barbara, California 93106-5080, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Smith
authors.affiliation: Department of Chemical Engineering, University of California Santa Barbara , Santa Barbara, California 93106-5080, United States.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Shell
authors.affiliation: Department for Interface Chemistry and Surface Engineering, Max-Planck-Institut für Eisenforschung GmbH , D-40237 Düsseldorf, Germany.|Department for Physical Chemistry, Technische Universität Bergakademie Freiberg , D-09599 Freiberg, Germany.
authors.forename: Markus
authors.identifier: 0000-0001-5410-1067
authors.initials: M
authors.lastname: Valtiner
keywords: AFM; Jarzynski’s equality; hydrophobic interaction; molecular dynamics; peptide; self-assembled monolayer; single-molecule force spectroscopy; steered molecular dynamics