Coupling among vesicles containing a chemical oscillating reaction in
microfluidics based devices
Raphaël Tomasia, Jean-Marc Noëlb, Sandra Ristoric, Federico Rossid, Valérie Cabuila, Frédéric Kanoufib
and Ali Abou-Hassana
a
Pierre et Marie Curie University, Paris, France; b Paris Diderot University, Paris, France; c University of
Florence, Florence, Italy; d University of Salerno, Fisciano (SA), Italy.
Generation, propagation and reception of (bio/chemical) information among individual organisms are the
keystone of many intelligent communicating systems and are ubiquitous in Nature. Fireflies’ colonies
flashes, contraction and expansion of heart muscles are only few examples among others, where
bio/chemical signals generated by synchronized sources produce a cooperative behaviour [1,2].
Here we propose an experimental model able to catch the essential features of the signal transmission
networks, characteristic at the basis of any complex living system. In particular, we will investigate coupled
chemical oscillators, such as the Belousov-Zhabotinsky (BZ) reaction, as a model for signal
transmission/reception between different confined compartments, i.e. single oscillators will be
compartmentalized in special reaction environments (vesicles) and their interaction will be monitored and
studied.
Figure 1. Left panel describes the oscillating mechanism of the BZ reaction: three key steps are the basic backbone of a much more
complex kinetic mechanism, briefly the concentration of Br- and of the oxidized form of the catalyst act as switchers among the three
processes, (A) Br- ions are consumed to yield bromine and bromous acid HBrO2, (B) the autocatalytic species HBrO2 oxidizes the
catalyst and (C) the catalyst is reduced by the organic substrate to yield Br- and restart the cycle. The squares in the corners illustrate
the colour and redox state changes of the catalyst (ferroin). Right panel: a spectrophotometric time-series (absorbance maximum of
ferroin) shows typical relaxation oscillations of the cycling reaction.
The BZ reaction consists of an oxidation of an organic substrate (generally malonic acid) by bromate ions in
a strongly acidic medium and in the presence of a redox catalyst (ferroin, cerium sulphate, ruthenium
complexes, etc.) [3,4]. Figure 1 briefly summarizes the basic mechanism responsible for the onset of the
oscillations in the concentration of some key intermediates, together with a typical spectrophotometric timeseries.
The appearance of complex temporal or spatio-temporal phenomena in coupled BZ reactions, has been
observed in different compartments such as lipid bilayers [5,6], arrays of BZ microdroplets [7,8], lattices
[9,10], bulk systems of catalyst-loaded resin microparticles [11,12] and lipid based emulsions [13–15].
However, if many reports have focused on a biomimetic approach on the dynamic and the collective
behaviour of droplets loaded with BZ, to the best of our knowledge, there have been no real attempts to study
the dynamic of the BZ reaction in artificial cell-like compartments such as liposomes, or trials to understand
how chemical information can cross the membrane of these liposomes to generate a chemical
communication between different compartments. Herein we report, for the first time, the encapsulation of the
BZ reaction as a source of chemical information inside liposomes in order to study the dynamic of the
oscillations and the transmission of the chemical information between such biomimetic compartments. The
encapsulation has been obtained by using a coaxial flow microfluidic device and the dynamics of signals
transmission across droplets has been recorded and analysed (see Figure 2). the results are supported by
interfacial electrochemical investigations on a bulky model of the liposomes in order to probe the
transmission of the chemical information across the interfaces.
!
Figure 2 Formation of the BZ/O/W double emulsions in the coaxial microlfuidc device: a) at the entrance of the collection capillary, b) at the
exit of the collection capillary, time elapsed 20 seconds. The BZ reagents were injected in the inner phase while the middle phase consisted
of 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) phospholipids dissolved in suitable and volatile organic solvents, the external
phase was a viscous aqueous solution of polyvinyl alcohol (PVA). Inner drops containing the BZ reactants were formed in the dripping
regime from a small injection tube while the middle oil stream containing the inner drops was flow-focused by the outer continuous phase.
At the outlet of the microdevice the solvent quickly evaporates and formed liposomes can freely float in a water solution. Panels c) – d) show
the pulses transmission across touching droplets. White arrows indicate the direction of the pulse propagation.
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