Designing DNA from scratch: Engineering the functions of micrometer-
sized DNA droplets

Date:
July 15, 2020
Source:
Tokyo Institute of Technology
Summary:
Scientists have constructed ''DNA droplets'' comprising designed
DNA nanostructures. The droplets exhibit dynamic functions such as
fusion, fission, Janus-shape formation, and protein capture. Their
technique is expected to be applicable to a wide variety of
biomaterials, opening doors to many promising applications in
materials design, drug delivery, and even artificial cell-like
molecular systems.



FULL STORY ==========================================================================
In living organisms, DNA is the storage unit of all genetic
information. It is with this information that proteins are encoded,
which then enable biological systems to function as needed for the
organism to survive. DNA's functioning is enabled by its structure:
a double-stranded helix formed via the joining of specific pairs of
molecules called 'nucleotides' in specific orders, called 'sequences'. In recent decades, scientists in the fields of DNA nanotechnology have been
able to design DNA sequences to construct desired nanostructures and microstructures, which can be used to investigate biomolecular functions
or create artificial cell systems.


==========================================================================
The customization of the designs of sequences in DNA nanotechnology
also enables the interactions among DNA molecules to be controlled
and programmed.

The inter-molecular interactions in cells cause various phenomena. A
phenomenon called "liquid-liquid phase separation (LLPS)" -- the
separation of a liquid into a denser phase of droplets within a
more dilute phase -- plays an important role in many biological
processes. LLPS artificially induced via DNA nanotechnology can help
deepen our understanding of the applicability of LLPS and provide a
methodology for controlling bio-macromolecular droplets.

Therefore, a team of scientists from Tokyo Tech, led by Professor Masahiro Takinoue, designed specific DNA-nanostructures to understand the influence
of DNA sequences and demonstrate controllability on LLPS -- into DNA-rich
and DNA- poor phases -- in artificially designed DNA nanostructures.

Their study, published in Science Advances, involved the construction of
Y- shaped DNA nanostructures called "Y-motifs." Each side of a Y-motif comprises a short sticky end that interacts with other 'compatible' sticky ends. Upon progressively decreasing the temperature, the scientists found
that the Y- motifs reversibly agglomerate to form droplets and then gels.

When they added another set of constructed Y-motifs with sticky ends
that are incompatible with the previous set, two sets of droplets were
formed for each type of Y-motif. This demonstrated that DNA sequences
can be tailored to fuse exclusively with similar ones.

Prof Takinuoe and team then created a special DNA structure that
can bridge together the incompatible Y-motifs. Upon adding this
to the mixture of Y- motifs, droplets composed of both motifs were
formed. Further construction of a cleavable variant of the special
bridge DNA structure and subsequent addition of a certain cleaving enzyme caused the fission of droplets and the mixed droplets to separate into Janus-shaped droplets with unmixable halves containing the two types
of Y-motif. By conjugating cargo molecules with DNA strands compatible
with either one type of Y-motif, the scientists were able to localize
the cargo molecules exclusively on one half of the droplet.

Thus, the scientists were able to 'program' DNA and 'control' their
behavior, opening doors to a new technique for creating artificial
reaction environments to study biological systems and drug delivery. Prof Takinoue explains: "Living systems are well-organized dynamic structures
whose behavior is regulated by the information encoded in biopolymers
(such as DNA). Our DNA-based liquid- liquid phase separation system could provide a new basis for the development of artificial cell engineering." Because precise DNA sequences can be readily produced using available bioengineering techniques, the potential applications of manipulating
material behaviors through DNA sequences are far-reaching. Prof Takinoue concludes: "The phase behavior shown in this study could be expanded
to other materials that can be modified with DNA, which may enable us
to design phases and create droplets for various materials. Moreover,
we envision that the observed autonomous behavior of macromolecular
structures could one day serve for the development of robotic molecular
systems comparable to those of living cells."

========================================================================== Story Source: Materials provided by Tokyo_Institute_of_Technology. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Yusuke Sato, Tetsuro Sakamoto, Masahiro Takinoue. Sequence-based
engineering of dynamic functions of micrometer-sized DNA droplets.

Science Advances, 2020; 6 (23): eaba3471 DOI: 10.1126/sciadv.aba3471 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200715131236.htm

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