Biology Reference
In-Depth Information
devices have been applied, in recent years, to the production of w/o droplets (which are
easy to make), in order to exploit the
(IVC) strategy (à la
Tawfik/Griffiths
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) for high-throughput screening the activity of proteins, genes, etc. for
directed evolution, and assay miniaturization, as well as for several physicochemical
investigations.
33
In contrast to the use of microfluidic devices for creating and manipulating
the w/o droplets, very few efforts have been reported on the application of microfluidic
technology to lipid vesicles (in particular GVs). In this respect, the final goal would be the
high-throughput production of GVs in a very reproducible manner, as already happens with
w/o droplets, and with the possibility of controlling their internal solution. Ideally, a
microfluidic device could produce GVs for biotechnological applications thanks to its
reliability in terms of the features described above. In other words, this would correspond to
a controllable and fully tunable
'
in vitro compartmentalization
'
To the best of our
knowledge, only five reports have been published dealing with the issue of producing GVs
by microfluidic devices. These have been reviewed in
11
, with a recent addition.
34
If these
methodologies, which are still young, are further developed in a robust way, they certainly
will improve our technological ability for constructing SSMCs, not necessarily living, for a
variety of applications.
lipid-vesicle-producing machine.
'
'
One of the most interesting applications refers to the construction of
bioreactors,
'
'
'
for intelligent drug delivery applications. In their
vision, Le Duc and coworkers
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foresee that a kind of SSMC is built by encapsulating a
minimal metabolic network capable of producing a drug. The drug production should occur
only when the SSMC has reached the target tissue inside the human body, for instance,
thanks to the specific addressing mechanism (e.g. by functionalizing the lipid vesicle with
antibodies that recognize specific antigens presented on the surface of the target tissue).
Then, the SSMC, by
nanofactories,
'
or
'
wet-soft bionanorobots
'
its environment, should trigger the intravesicle drug
production, and its exportation in the external environment. From there, the drug should
diffuse into the target cell and exert a pharmacological effect. It is interesting to note that
several of the functions required for the construction of such nanofactories are typical
functions that are also important in basic research on SSMCs. Possibly, therefore, the
knowledge acquired in basic research will be applied to design and construct advanced
SSMCs for specific biotechnological applications. Remarkably, the sensing function and the
corresponding activation of an internal response bring us directly to the concepts of control
and communications.
sensing
'
'
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Quite recently, we argued that the technology of SSMCs can be useful for developing new
tools in bio-inspired information and communication technology (bio-ICT). In particular,
we have proposed an experimental program for letting synthetic cells communicate with
natural cells, via chemical signals.
36
The experimental model to start with would be the
development of a chemical language that is common with bacteria, for instance based on
acyl homoserine lactones (AHLs), signaling peptides, or furanones. We plan to develop
SSMCs step-wise that can send signals to living cells, like in the first pioneer work,
published in 2009 by the group of Davis.
37
With this aim, SSMCs should produce AHLs by
expressing the corresponding synthase (e.g. via the PURE system). AHLs, once synthesized,
can freely diffuse away and reach the receiving (living) cell, activating the expression of a
reporter gene. Conversely, SSMCs can be designed in order to express a receptor for sensing
a signal molecule sent by the natural partner. After being activated by the chemical signal
(also in this case it is convenient to use AHLs), the receptor allows the transcription of a
reporter gene. Both the receptor and the reporter gene will be expressed by transcription/
translation kits, like the PURE system. Next, we plan to combine these mechanisms for
establishing bidirectional synthetic cell
natural cell communication, and after this,
synthetic communication between synthetic cells. It is remarkable that this research
program implies that SSMCs can be used as computing entities that could lead to new
forms of bio-ICTs.
