Biomedical Engineering Reference
In-Depth Information
consequently the signature blocks became barely detected. Overall, the signature
blocks can be used to distinguish a TBA molecule either in the G-quartet form or
linear form.
3.2.2 Spontaneous Unfolding of the G-Quadruplex
in the Nanocavity
The most significant finding is that the signature block is terminated with a spike-like
full block (Fig.
3.4b
traces), which is similar to the short events for linear formDNA
translocation in conductance and duration [
99
]. This current profile represents such
a molecular process that the encapsulated G-quadruplex spontaneously unfolds into
a linear DNA that immediately traverses the
-barrel (Fig.
3.4b
left model). The
unfolding is likely to occur spontaneously, as the electrical field in the nanocavity,
which is much weaker than in the
b
b
-barrel, has little impact on the G-quadruplex.
3.2.3
Interaction of Nanopore with the Trapped
G-Quadruplex
The interaction of nanopore with the trapped G-quadruplex can be revealed using
a designed TBA variant, called tag-TBA that contains a GACTAC tag at the
5
0
terminal [
99
]. When folded, the tag-TBA form a ball (quadruplex)-stick (tag)
chimera (Fig.
3.4c
). The tag-TBA not only generates the TBA signature blocks, but
also produces a series of new Level-2 blocks upon the signature block (Fig.
3.4c
left).
Since the conductance of Level-2 blocks is similar to that for linear form DNA
translocation, they are expected to be caused by the interaction of the linear tag
with the
b
-barrel, therefore verifying that the tag-TBA is accommodated around
the bottom of the nanocavity, where it vibrates, repeatedly touching the entry of the
b
-barrel, producing reversible Level-2 blocks. In addition, the Level-2 blocks can
also occasionally disappear (Fig.
3.4c
right), marking a movement that the tag-TBA
suddenly rotates to another orientation within the nanocavity, leaving the
b
-barrel
untouched by the tag-TBA bottom.
3.2.4 Analytical Approach to Learning Folding/Unfolding
Kinetics
The G-quadruplex folding/unfolding kinetics can be quantitatively dissected using
a mathematic approach [
100
]. Firstly, the duration of the signature block
has been
proven to be the lifetime of the G-quadruplex in the solution. By comparing
t
in
different ions, we can understand the role of ion in the G-quadruplex stability. For
t
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