Fiche publication
Date publication
mars 2019
Journal
The journal of physical chemistry. B
Auteurs
Membres identifiés du Cancéropôle Est :
Dr NICOLAI Adrien
,
Dr DELARUE Patrice
,
Pr SENET Patrick
Tous les auteurs :
Nicolaï A, Barrios Pérez MD, Delarue P, Meunier V, Drndić M, Senet P
Lien Pubmed
Résumé
Solid-state nanopores (SSN) made of two-dimensional materials such as molybdenum disulfide (MoS) have emerged as candidate devices for biomolecules sequencing. SSN sequencing is based on measuring the variations in ionic conductance as charged biomolecules translocate through nanometer-sized channels, in response to an external voltage applied across the membrane. Although several experiments on DNA translocation through SSNs have been performed in the past decade, translocation of proteins has been less studied, partly due to small protein size and detection limits. Moreover, the threading of proteins through nanopore channels is challenging, because proteins can exhibit neutral global charge and not be sensitive to the electric field. In this paper, we investigate the translocation of lysine residues and a model protein with polylysine tags through MoS nanoporous membranes using molecular dynamics simulations. Adding lysine tags to biological peptides is the method proposed here to promote the entrance of proteins through SSN. Specifically, we study the relationship existing between the translocation events and the ionic conductance signal drops. We show that individual lysine residues translocate easily through MoS nanopores, but the translocation speed is extremely fast, which leads to indiscernible ionic conductance drops. To reduce the translocation speed, we demonstrate that increasing the thickness of the membrane from single-layer to bilayer MoS reveals a stepwise process of translocation with discernible conductance drops that could be measured experimentally. Finally, a study of the threading of proteins with polylysine tags through MoS nanopores is presented. The addition of the positively charged tag to the neutral protein allows the threading and full translocation of the protein through the pore (at least two lysine residues are necessary in this case to observe translocation) and a similar sequence of translocation events is detected, independently of the tag length.
Mots clés
Disulfides, chemistry, Membranes, Artificial, Molecular Dynamics Simulation, Molybdenum, chemistry, Nanopores, Polylysine, chemistry, Protein Transport, Sequence Analysis, Protein
Référence
J Phys Chem B. 2019 03 14;123(10):2342-2353
