title: Acidity-Mediated, Electrostatic Tuning of Asymmetrically Charged Peptides Interactions with Protein Nanopores.
abstract: Despite success in probing chemical reactions and dynamics of macromolecules on submillisecond time and nanometer length scales, a major impasse faced by nanopore technology is the need to cheaply and controllably modulate macromolecule capture and trafficking across the nanopore. We demonstrate herein that tunable charge separation engineered at the both ends of a macromolecule very efficiently modulates the dynamics of macromolecules capture and traffic through a nanometer-size pore. In the proof-of-principle approach, we employed a 36 amino acids long peptide containing at the N- and C-termini uniform patches of glutamic acids and arginines, flanking a central segment of asparagines, and we studied its capture by the α-hemolysin (α-HL) and the mean residence time inside the pore in the presence of a pH gradient across the protein. We propose a solution to effectively control the dynamics of peptide interaction with the nanopore, with both association and dissociation reaction rates of peptide-α-HL interactions spanning orders of magnitude depending upon solution acidity on the peptide addition side and the transmembrane electric potential, while preserving the amplitude of the blockade current signature.
authors.affiliation: †Department of Interdisciplinary Research, Alexandru I. Cuza University, Iasi, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Asandei
authors.affiliation: ‡Center for Life Nano Science, Istituto Italiano di Tecnologia, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Chinappi
authors.affiliation: §Department of Biomedical Science and Research Center for Proteineous Materials, Chosun University, Gwangju, South Korea.
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
authors.affiliation: ∥Department of Bioinformatics, Kongju National University, Kongju, South Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Seo
authors.affiliation: ⊥Department of Physics, Alexandru I. Cuza University, Iasi, Romania.
authors.forename: Loredana
authors.initials: L
authors.lastname: Mereuta
authors.affiliation: §Department of Biomedical Science and Research Center for Proteineous Materials, Chosun University, Gwangju, South Korea.
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Park
authors.affiliation: ⊥Department of Physics, Alexandru I. Cuza University, Iasi, Romania.
authors.forename: Tudor
authors.initials: T
authors.lastname: Luchian
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008422:Materials Testing; D008956:Models, Chemical; D058608:Nanopores / Q000648:ultrastructure*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D055672:Static Electricity
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D011506:Proteins
keywords: biotechnology; control of peptide dynamics; lipid bilayer interfaces; nanoscale peptide trafficking; protein nanopore; single-molecule electrophysiology