Metabolic soft matter with life-like properties

Informations projet

MeSoMat

N° de convention de subvention: 770940

DOI

10.3030/770940

Projet clôturé

Date de signature de la CE 15 Mai 2018

Date de début 1 Juin 2018

Date de fin 31 Mai 2024

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 899 333,00

Contribution de l’UE

€ 1 899 333,00

Coordonné par

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 4 - MeSoMat (Metabolic soft matter with life-like properties)

Période du rapport: 2022-12-01 au 2024-05-31

Résumé du contexte et des objectifs généraux du projet

A fundamental difference between man-made and living matter is metabolism: the ability to dissipate chemical energy to drive many different chemical processes out of equilibrium. Metabolism endows chemical systems within living organisms with properties that are standard in biology but odd in chemistry: the capability to process information, to move and to react to the external world.

The goal of the MESOMAT project is to endow soft materials with dynamic life-like properties. We have chosen four: molecular computation, movement, self-construction and the capacity to entertain complex chemical conversations with living cells. The underlying idea is embed stimuli-responsive materials with a biocompatible synthetic metabolism capable of sustaining autonomous chemical feedback loops that process information and perform autonomous macroscopic actions. The MESOMAT approach combines concepts from systems chemistry, synthetic biology and DNA molecular programming with soft materials and uses a biochemical system that we have contributed to pioneer: DNA/enzyme active solutions that remain out of equilibrium by consuming a chemical fuel with non-trivial reaction kinetics. This system has three unique properties: programmability, biocompatibility and a long-term metabolic autonomy.

Metabolic matter will be assembled in two stages: i) enabling metabolic materials with dynamic chemical, biological and mechanical responses, and ii) creating metabolic materials with unprecedented properties, in particular, the capacity of self-construction, which I will seek by emulating embryogenesis, and the ability to autonomously pattern a community of living cells. By doing this I will create for the first time chemical matter that is both dynamically and structurally complex, thus bringing into the realm of synthetic chemistry behaviours that so far only existed in biological systems. In the long term, metabolic matter could provide revolutionary solutions for soft robotics and tissue engineering.

MESOMAT has succeeded its main objectives. We have been able to combine out-of-equilibrium DNA molecular programs with molecular and cellular outputs, in particular with molecular motors and eukaryotic cells. We have also been able to implement chemo-mechanical and mechanochemical couplings in such materials, implementing synthetically behaviours that exist in living embryos. We have discovered a new class of structuration mechanism in active matter and we have use this knowledge to scaffold materials whose intrinsic dynamic complexity unfolds into structural complexity.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Our work has focused on two broad types of systems: i) Active solutions that pattern living cells and ii) DNA-cytoskeletal active fluids and gels. We have obtained and published remarkable results along these two lines. Concerning the first subject, we have devised a DNA program that controls the internalization of fluorescent DNA inside living cells (Van der Hofstadt et al, ACS nano. 2021). We thus have shown that a self-organized pattern of DNA can transfer its positional information to living cells, even in the presence of extracellular media (Galas et al, ACS synth. biol. 2022). This is the first time that a DNA program runs in the presence of living cells.

Concerning the second subject, we have first thoroughly investigated pattern formation in cytoskeletal active gels and demonstrated the importance of both passive and active forces in shaping active matter and demonstrate that a spontaneously flowing active fluid can be sculpted into a static material through an active mechanism (Senoussi et al, PNAS 2019, Sarfati et al, Soft Matter 2022). Then, we have coupled these active systems with DNA molecular programs making mechano-chemical (Senoussi et al, Sci. Adv. 2021) and chemo-mechanical (Vyborna et al, JACS 2021) couplings, inspired from embryo development. We have also theoretically investigated such chemo-mechanical coupling (Del Junco et al, Phys. Rev. E, 2022).

We have also worked on complex pattern formation with high spatial resolution where we have obtained and published good results (Urtel et al, Soft matter, 2019).

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

- Observation of a new spatial instability in motor-filament active fluids (Senoussi et al, PNAS, 2019) and full description of the determinants of pattern formation in motor-filament active fluids ( Sarfati et al, Soft Matter 2022.
- First demonstration of Spatiotemporal Patterning of Living Cells with Extracellular DNA Programs (Van Der Hofstadt et al, ACS nano 2021).
- Experimental implementation of mechano-chemical (Senoussi et al, Sci. Adv. 2021) and chemo-mechanical (Vyborna et al, JACS 2021) couplings, inspired from embryo development.

mechano-chemical-transduction.png

Confocal image of a corrugated sheet of microtubule filaments.

Scheme of DNA/enzyme extracellular media to culture human cells.