Morphogenesis in molecular systems
DNA nanotechnology, Molecular programming, Morphogenetic matter

Our research

Symbiosis

We are engineering synthetic chemical systems that reproduce essential dynamic features of networks and populations in biology. The objective of our biomimetic approach is two-fold. On the one hand, by studying simple, physics-like and controllable molecular systems that retain the essential features of their biological analogues we hope to provide new insights on the emergence of complex biological behaviors -such as gene regulation, and morphogenesis. On the other hand, these dynamic molecular systems can be regarded as a new kind of "life-like" materials capable of adapting and responding autonomously to their environment.

To this end we essentially use systems based on nucleic acid hybridization reactions because their reactivity can be easily predicted by, roughly, Watson-Crick pairing rules. More precisely we work with four (mainly 1 and 2, see figure below) powerful and complementary experimental systems.

  • 1) The PEN DNA toolbox, a molecular programming language based on short DNA strands and three enzymes that can be kept out of equilibrium for tens of hours.
    The original developers of the PEN DNA toolbox present here in detail the system.

  • 2) The microtubule/kinesin system, a versatile active matter system that performs chemo-mechanical transductions.
    Two seminal papers from Nédélec et al., 1997, and Sanchez et al., 2012, can be found here and here.

  • 3) Cell-free transcription translation systems to study in vitro de dynamics of gene regulatory networks.

  • 4) DNA self-assembled nanostructures called DNA origami.


Symbiosis


We are currently focusing our efforts on the coupling of the two first mechanisms, the biochemical patterning using DNA/enzyme-based reaction and the generation of large scale mechanical forces using the microtubule/kinesin active matter.


Symbiosis

Over the last year, we successfully implemented a mechano-chemical transduction in vitro that mimics key aspects of the polarization mechanism observed in C. elegans oocytes. In an experimental configuration where the active gel contracts globally, homogeneously distributed DNA-coated beads are pulled and aggregated in the center of the reactor. Encoding a density-dependent bistable reaction network, we were able to make this contraction trigger the propagation of a biochemical DNA front, as depicted in the left panel above (a). This is reminiscent of the asymmetric contraction of the actomyosin cortex in the C. elegans embryo, which transports specific proteins of the partitioning system (PAR protein family)) and thus induces the polarization of the embryo. A preprint of this work can be found in here.

In addition to this mechano-chemical transduction, we have made progress in obtaining a chemo-mechanical transduction. For this purpose, we designed kinesin molecular motor clusters that include a DNA strand. Through complementarity, this DNA strand makes it possible to retain the motor aggregates on a DNA coated surface. The addition of a suitable DNA strand, by strand displacement mechanism, releases the motor clusters into the solution. This triggers the self-organization of the microtubules. As the concentration of the motors influences the final self-organization of the system, the addition of a gradient of this releasing DNA, which could be called a morphogen, thus induces a spatialized self-organization as can be seen on the right (b).

We further develop microfluidic and micropatterning techniques for the spatial and temporal control of these reactive systems.



Below is an example of DNA-based reaction-diffusion fronts ignitiated from both sides. Encoded through different sequences, they do not collide.

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More complex: a DNA-based predator-prey network. Waves of preys (yellow) and predators (green) are observed for hours in a closed ring.


Below, a 3D solution of kinesin motors and microtubule filaments spontaneously forms a 2D free-standing nematic active sheet that actively buckles out-of-plane into a centimeter-sized periodic corrugated sheet. On top, the final structure is a corrugated sheet, at the bottom, the corrugated sheet (stripes at 60 min) is transient.