Farimani, A. Barati; Heiranian, M.; Aluru, N. R.
Electromechanical Signatures for DNA Sequencing through a Mechanosensitive Nanopore
JOURNAL OF PHYSICAL CHEMISTRY LETTERS, 6:650-657, FEB 19 2015

Biological nanopores have been extensively used for DNA base detection since these pores are widely available and tunable through mutations Distinguishing bases of nucleic acids by passing them through nanopores has so far primarily relied on electrical signals specifically, ionic currents through the nanopores. However, the low signal-to-noise ratio makes detection of ionic currents difficult In this study, we show that the initially closed mechanosensitive channel of large conductance (MscL) protein pore opens for single-stranded DNA (ssDNA) translocation under an applied electric field. As each nucleotide translocates through the pore, a unique mechanical signal is observed specifically, the tension in the membrane containing the MscL pore is different for each nucleotide. In addition to the membrane tension, we found that the ionic current is also different for the four nucleotide types. The initially closed MscL adapts its opening for nucleotide translocation due to the flexibility of the pore. This unique operation of MscL provides single nucleotide resolution in both electrical and mechanical signals. Finally, we also show that the speed of DNA translocation is roughly 1 order of magnitude slower in MscL compared to Mycobacterium smegmatis porin A (MspA), suggesting MscL to be an attractive protein pore for DNA sequencing.

DOI:10.1021/jz5025417

Find full text with Google Scholar.