Counting polymers moving through a single ion channel

Abstract

THE change in conductance of a small electrolyte-filled capillary owing to the passage of sub-micrometre-sized particles has long been used for particle counting and sizing. A commercial device for such measurements, the Coulter counter, is able to detect particles of sizes down to several tenths of a micrometre^1–3. Nuclepore technology (in which pores are etched particle tracks) has extended the lower limit of size detection to 60-nm particles by using a capillary of diameter 0.45 μm (ref. 4). Here we show that natural channel-forming peptides incorporated into a bilayer lipid membrane can be used to detect the passage of single molecules with gyration radii as small as 5–15 Å. From our experiments with alamethicin pores we infer both the average number and the diffusion coefficients of poly(ethylene glycol) molecules in the pore. Our approach provides a means of observing the statistics and mechanics of flexible polymers moving within the confines of precisely defined single-molecule structures.