TY - JOUR
T1 - Smooth DNA transport through a narrowed pore geometry
AU - Carson, Spencer
AU - Wilson, James
AU - Aksimentiev, Aleksei
AU - Wanunu, Meni
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (R21-HG006873 and R01-HG006321, M.W.; R01-HG007406; NSF DMR-0955959 A.A. and J.W.). The authors gladly acknowledge supercomputer time provided through XSEDE Allocation Grant MCA05S028 and the Blue Waters petascale supercomputer system (UIUC).
Publisher Copyright:
© 2014 Biophysical Society.
PY - 2014/11/18
Y1 - 2014/11/18
N2 - Voltage-driven transport of double-stranded DNA through nanoscale pores holds much potential for applications in quantitative molecular biology and biotechnology, yet the microscopic details of translocation have proven to be challenging to decipher. Earlier experiments showed strong dependence of transport kinetics on pore size: fast regular transport in large pores (> 5 nm diameter), and slower yet heterogeneous transport time distributions in sub-5 nm pores, which imply a large positional uncertainty of the DNA in the pore as a function of the translocation time. In this work, we show that this anomalous transport is a result of DNA self-interaction, a phenomenon that is strictly pore-diameter dependent. We identify a regime in which DNA transport is regular, producing narrow and well-behaved dwell-time distributions that fit a simple drift-diffusion theory. Furthermore, a systematic study of the dependence of dwell time on DNA length reveals a single power-law scaling of 1.37 in the range of 35-20,000 bp. We highlight the resolution of our nanopore device by discriminating via single pulses 100 and 500 bp fragments in a mixture with >98% accuracy. When coupled to an appropriate sequence labeling method, our observation of smooth DNA translocation can pave the way for high-resolution DNA mapping and sizing applications in genomics.
AB - Voltage-driven transport of double-stranded DNA through nanoscale pores holds much potential for applications in quantitative molecular biology and biotechnology, yet the microscopic details of translocation have proven to be challenging to decipher. Earlier experiments showed strong dependence of transport kinetics on pore size: fast regular transport in large pores (> 5 nm diameter), and slower yet heterogeneous transport time distributions in sub-5 nm pores, which imply a large positional uncertainty of the DNA in the pore as a function of the translocation time. In this work, we show that this anomalous transport is a result of DNA self-interaction, a phenomenon that is strictly pore-diameter dependent. We identify a regime in which DNA transport is regular, producing narrow and well-behaved dwell-time distributions that fit a simple drift-diffusion theory. Furthermore, a systematic study of the dependence of dwell time on DNA length reveals a single power-law scaling of 1.37 in the range of 35-20,000 bp. We highlight the resolution of our nanopore device by discriminating via single pulses 100 and 500 bp fragments in a mixture with >98% accuracy. When coupled to an appropriate sequence labeling method, our observation of smooth DNA translocation can pave the way for high-resolution DNA mapping and sizing applications in genomics.
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U2 - 10.1016/j.bpj.2014.10.017
DO - 10.1016/j.bpj.2014.10.017
M3 - Article
C2 - 25418307
AN - SCOPUS:84912094881
VL - 107
SP - 2381
EP - 2393
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 10
ER -