Electro-Osmotic Driven Kinetics of Cyclodextrin through the CymA Channel

Abstract

Trans membrane voltage is applied to understand the permeation of uncharged molecules into and across nano pores in Electrophysiology. The permeating molecule blocks the ion flow causing ion current fluctuations. However the fluctuation density is dependent on the magnitude and direction of the applied voltage. This dependency may be assumed due to electro-osmotic (EOF) flow, electrically driven ion – associated water flow. Here we investigate the contribution of the electro-osmotic flow (EOF) as a potential cause for an external voltage driven substrate permeation. As an example, we quantified the permeation of α-cyclodextrin through the cyclodextrin-specific channel-forming porin CymA from the Gram-negative bacterium Klebsiella oxytoca. To further elucidate these effects, substrate interaction studies were performed at various external voltages in presence of three different electrolyte solutions: KCl, NaCl and MgCl2. To demonstrate the significance of the EOF at an atomistic level, the net water flux was calculated and its effect on the binding affinity of substrates was studied by employing extensive molecular dynamics simulations.[1] B. van den Berg et al., Proceedings of the National Academy of Sciences, 112, E2991-E2999 (2015).[2] F. Orlik et al., Biophysical journal, 85, 876–885 (2003).[3] L.-Q. Gu et al., Proceedings of the National Academy of Sciences, 100, 15498–15503 (2003).