Biomedical Engineering Reference
In-Depth Information
5.1
DNA-Based Molecular Architectures
Usually, molecular architectures are modular, i.e., composed of basic building
blocks called tiles. The design of tiles depends on the application. For instance,
the DNA scaffold could be flexible or rigid, dynamic or static, symmetric or
asymmetric, potentially infinite or of a certain dimension. Therefore, one must take
into account the properties of biological components, for example, single-strand
DNA (ssDNA) and double-strand DNA (dsDNA), as well as the interconnections
between them that allow their assembly into tiles and more complicated structures.
A DNA strand has two ends, denoted by 5 0 and 3 0 , which confer a natural
orientation to the DNA molecule, such that two complementary ssDNA strands
bind in an antiparallel way with respect to these ends. The DNA double helix has
a diameter of 2 nm and a helical repeat of 3.4 nm, corresponding to 10.5 bases.
As a rule, ssDNA molecules are very flexible and can form tight loop structures,
while dsDNA is quite rigid in short strands, up to 150 bp, and flexible if longer
( Feldkamp and Niemeyer 2006 ). ssDNA is used as a template or, especially when
immobilized, as capture probe for specific self-assembly of other molecules tagged
with complementary base sequences.
The linear dsDNA molecule is still not rigid enough to form two- or three-
dimensional structures. More complex DNA-based molecules are needed for this
purpose, such as branched junction motifs with three and four arms, which consist
of dsDNA helices. These structures, in which the helical arms are connected at the
central branching point, are illustrated in Fig. 5.1 , different helices being represented
with different colors. Branch migration around the branching point is avoided by
appropriately choosing the base sequences of all arms.
Branched DNA molecules can form more complex structures by the inclusion
of internal loops, which consist of unpaired bases, in the strands (see Fig. 5.1 c) or
the addition of a bulge to only one strand at the branching point. In the last case,
the angle between the helical arms changes to about 180 ı , as illustrated in Fig. 5.1 d.
Cyclic structures in which at least one of the helical arm axes does not point towards
the center of the junction form knots ( Seeman 1998 ; Feldkamp and Niemeyer 2006 ).
Branched molecules are still conformational flexible so that several such
molecules must be linked together in even more rigid structures, called lattices.
A branched DNA molecule links to another one through sticky ends. These unpaired
a
b
c
d
Fig. 5.1 Branched DNA junction motifs: ( a ) three-arm junction, ( b ) four-arm junction, ( c ) three-
arm junction with internal loop, ( d ) bulged three-arm junction
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