Disentangling Steric and Electrostatic Factors in Nanoscale Transport Through Confined Space

Abstract

The voltage-driven passage of biological polymers through nanoscale pores is an analytically, technologically, and biologically relevant process. Despite various studies on homopolymer translocation there are still several open questions on the fundamental aspects of the pore transport. One of the most important unresolved issues revolves around the passage of biopolymers which vary in charge and volume along their sequence. Here we exploit an experimentally tunable system to disentangle and quantify electrostatic and steric factors. This new, fundamental framework facilitates the understanding of how complex biopolymers are transported through confined space and indicates how biopolymer translocation can be slowed down to enable future sensing methods.SYNOPSIS: The voltage-driven translocation of complex biopolymers through a protein nanopore is biophysically modeled to disentangle and quantify electrostatic and steric factors which can oppose electrophoretic movement.

Discrimination of supramolecular chirality using a protein nanopore

“…Thus, unambiguous assignment of cage chirality was only possible using ion current blockages that result from electrostatic and steric factors, which are difficult to predict. 43 …”

Electrostatic Forces in Field-Perturbed Equilibria: Nanopore Analysis of Cage Complexes

“…Indeed, the chiral forms of the positively charged cages were not resolved due to the small current blockages for such species (Ib/Io = 0.89-0.93, Figures 2,3A). Although the magnitudes of ion current blockages are complicated by multiple determining factors, 54 the relatively small current blockages for both cationic and anionic cages indicate that the transient bind of cages occurs at the cis-entrance of the nanopore, rather than deep within the pore vestibule.…”

“…An indication of the local electrostatic interactions can be obtained by visualizing the surface charges of the -hemolysin protein nanopore and the electrostatic potentials of the cages. 54 The nanopore was calculated [59][60][61] to have a net charge of +7.0 at pH 8.0 that is distributed non-homogeneously over the protein (Figure 4 and S4). Meanwhile, the charges on the cages are both more intense and relatively homogenous ( Figure S5).…”

Comparative analysis of nucleotide translocation through protein nanopores using steered molecular dynamics and an adaptive biasing force

“…The translocation system we have chosen to investigate is the passage of nucleotide molecules through the protein nanopore α‐hemolysin (αHL), depicted in Figure . αHL is a heptameric protein‐pore that has been extensively studied in experiments and computer simulations, and is the biological pore currently in use in the developing technologies at Oxford Nanopore . We explore the protein‐pore translocation of the nucleic acid strands polyadenosine, poly(A), and polydeoxycytidine, poly(dC), which are single strands of RNA and DNA, respectively.…”