Probing single nanometer-scale pores with polymeric molecular rulers.

We previously demonstrated that individual molecules of single-stranded DNA can be driven electrophoretically through a single Staphylococcus aureus alpha-hemolysin ion channel. Polynucleotides thread through the channel as extended chains and the polymer-induced ionic current blockades exhibit stable modes during the interactions. We show here that polynucleotides can be used to probe structural features of the alpha-hemolysin channel itself.

Nanoscopic porous sensors.

There are thousands of different nanometer-scale pores in biology, many of which act as sensors for specific chemical agents. Recent work suggests that protein and solid-state nanopores have many potential uses in a wide variety of analytical applications. In this review we survey this field of research and discuss the prospects for advances that could be made in the near future.

Single-molecule mass spectrometry in solution using a solitary nanopore.

We introduce a two-dimensional method for mass spectrometry in solution that is based on the interaction between a nanometer-scale pore and analytes. As an example, poly(ethylene glycol) molecules that enter a single alpha-hemolysin pore cause distinct mass-dependent conductance states with characteristic mean residence times. The conductance-based mass spectrum clearly resolves the repeat unit of ethylene glycol, and the mean residence time increases monotonically with the poly(ethylene glycol) mass.

Functional reconstitution of protein ion channels into planar polymerizable phospholipid membranes.

We demonstrate that polymerizable planar membranes permit reconstitution of protein ion channels formed by the bacterial toxins Staphylococcus aureus alpha-hemolysin (alphaHL) and Bacillus anthracis protective antigen 63. The alphaHL channel remained functional even after membrane polymerization. Surface pressure measurements suggest that the ease of forming membranes depends on membrane surface elasticity estimated from Langmuir-Blodgett monolayer pressure-area isotherms.