title: Role of Electroosmosis in the Permeation of Neutral Molecules: CymA and Cyclodextrin as an Example.
abstract: To quantify the flow of small uncharged molecules into and across nanopores, one often uses ion currents. The respective ion-current fluctuations caused by the presence of the analyte make it possible to draw some conclusions about the direction and magnitude of the analyte flow. However, often this flow appears to be asymmetric with respect to the applied voltage. As a possible reason for this asymmetry, we identified the electroosmotic flow (EOF), which is the water transport associated with ions driven by the external transmembrane voltage. As an example, we quantify the contribution of the EOF through a nanopore by investigating the permeation of α-cyclodextrin through CymA, a cyclodextrin-specific channel from Klebsiella oxytoca. To understand the results from electrophysiology on a molecular level, all-atom molecular dynamics simulations are used to detail the effect of the EOF on substrate entry to and exit from a CymA channel in which the N-terminus has been deleted. The combined experimental and computational results strongly suggest that one needs to account for the significant contribution of the EOF when analyzing the penetration of cyclodextrins through the CymA pore. This example study at the same time points to the more general finding that the EOF needs to be considered in translocation studies of neutral molecules and, at least in many cases, should be able to help in discriminating between translocation and binding events.
authors: Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
authors: Satya Prathyusha
authors: SP
authors: Bhamidimarri
authors: Department of Physics and Earth Sciences, Jacobs University Bremen, Bremen, Germany.
authors: Jigneshkumar Dahyabhai
authors: JD
authors: Prajapati
authors: Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Bert
authors: B
authors: van den Berg
authors: Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
authors: Mathias
authors: M
authors: Winterhalter
authors: Department of Physics and Earth Sciences, Jacobs University Bremen, Bremen, Germany. Electronic address: u.kleinekathoefer@jacobs-university.de.
authors: Ulrich
authors: U
authors: Kleinekathöfer
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D053841:Electroosmosis; D041121:Klebsiella oxytoca / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data
chemical_list: D001425:Bacterial Outer Membrane Proteins; D003505:Cyclodextrins