Mechanism of Ionic Current Blockades during Polymer Transport through Pores of Nanometer Dimensions

Abstract

Linear anionic polymers driven through the α-hemolysin channel produce ionic current blockades. Three parameters of the blockades can be measured, including blockade amplitude, duration and modulations of amplitude within a single event. To test the hypothesis that blockade amplitude is related to the molecular volume of a linear polymer traversing the pore, the effects of four different polymers on the ionic current flowing through single α-hemolysin channels were compared. The amplitude of the blockade is proportional to the fraction of the pore volume occupied by the translocating polymer. We conclude that the primary contribution to the amplitude of a blockade is molecular volume, although other factors may also play minor roles. These results suggest that single nucleotide resolution will require a pore volume near the size of the individual monomers in a polynucleotide (~ 0.3 nm3), which will require an improvement of nearly two orders of magnitude over the current limiting volume provided by the α-hemolysin pore (~ 18 nm3).