Biomedical Engineering Reference
In-Depth Information
Fig. 12.8 MD simulation of the nanopore trap. (a) Snapshot of the system that includes
dsDNA
,
water and ions (not shown) as well as a 2.0 nm diameter pore. The molecular conformation within
the constriction is stretched beyond 0.34 nm/base-pair by 20-30%. (b) The number of base-pairs
permeating through the larger or the smaller pore in 4 MD simulations done at different biases. The
simulations predict a threshold between 500 mV and 1.0 V. (
Inset
) Histogram of the displacement
of the base-pair nearest to the membrane's center at a 0 V bias. The
solid line
shows the
distribution expected for a harmonic trap with a 7.2 nN/nm spring constant. (c) MD simulation
showing stepwise transport of
dsDNA
. A square-wave bias was applied to produce 1 and 2 base
pair step transport separated by a 2 ns rest interval through a 2.3
2.3 nm
2
pore. Adapted from
reference [
21
]
Using the Stokes' formula
is the viscosity of water, and
expressing the mean force as the time average of the instantaneous force, we find
<
x ¼
6
pZr
h
, where
Z
|
2
0.034 nN
2
, where
10 ns is the time interval of the
average. Thus, the rms-force is ~180 pN. Even if all of this force is transferred to the
DNA residing in the pore, which is unlikely due to the finite speed of the stress
propagation, the magnitude of the force will still be insufficient to displace the DNA
out of the trap shown in the MD simulations.
This potential could be used to control the motion of the
dsDNA
in the pore as
illustrated by the preliminary analysis given in Fig.
12.8c
. In these MD simulations,
with the application of a 0.11 ns duration 2 V square-wave pulse followed by 2 ns at
0 V (blue), the
dsDNA
is clearly conveyed through the pore in base-pair steps,
although sometimes it slides back and skips steps, presumably because the voltage
profile is not quite optimal. Two base-pair step are produced using a 0.12 ns pulse.
Thus, it seems feasible that
dsDNA
can be stepped through the pore in single base-
pair step under optimal conditions.
The current fluctuations associated with the trapped
|
F
> ¼
36
pZ
k
B
T
r
h
/
t ¼
t ¼
-DNA observed at low
voltage shown in the inset to Fig.
12.7c
and tallied in the histogram of Fig.
12.7e
support the hypothesis that the pore current can be used to detect the sequence of
base-pairs. We observed that for
t <
l
58.8 s the amplitude of the current fluctuations
increases relative to the open pore value found for longer times. With the molecule
trapped (i.e. for
t <
58.8 s in Fig.
12.7c
), we filtered the current data and formed
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