Artificial microtubules based on switchable cyclic peptides

Informations projet

CYCLOTUBES

N° de convention de subvention: 890659

DOI

10.3030/890659

Projet clôturé

Date de signature de la CE 5 Mars 2020

Date de début 5 Avril 2020

Date de fin 4 Avril 2022

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 184 707,84

Contribution de l’UE

€ 184 707,84

Coordonné par

UNIVERSITE DE STRASBOURG
France

Periodic Reporting for period 1 - CYCLOTUBES (Artificial microtubules based on switchable cyclic peptides)

Période du rapport: 2020-04-05 au 2022-04-04

Résumé du contexte et des objectifs généraux du projet

Natural systems from microscopic scale like bacteria to ultra big scales like river channels and mountain chains consist of very sophisticated designs and patterns marveling the human mind. The precision and efficiency of such natural systems has evolved over millions of years of error and rectification. Scientists always derive their inspiration from such complicated machineries present in nature and try to emulate the clockwork precision and functionalities present in biological systems to create useful artificial materials which could be beneficial for the humankind. We draw inspiration of from microscopic machineries in our cell which are able function with utmost precision and are vital for sustaining life. One such system are microtubules in our cell responsible for very important functions such as cell division and motility without which life cannot advance. Microtubules are long chains of smaller building blocks which only come together and assemble under certain conditions and dissociate when not required. Important characteristic of these systems is that they operate like any other sophisticated machinery where they only get transiently activated in presence of fuel(chemicals) which they use to do their work while producing waste and in absence of fuels they go dormant. They can continue doing this process for very prolonged period of time and thus sustain the vital functions in our cells. We term this process of fuel dependent activation and function as non-equilibrium self-assembly. We want to create such fuel dependent systems which can mimic naturally occurring machineries in our body and can grow, divide and disappear in response to the chemical signals given to them. This will allow much deeper understanding of natural processes occurring in our body while we might be able to use such precise functional life-like systems for many useful applications as mentioned before beneficial for the humankind.

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

The work was divided in 4 work packages where peptide based systems were developed. These systems could assemble and disassemble in response to chemical signals while mimicking microtubules forming tube like structures at nano-scopic scales. Such tubular artificial systems and not well known for their responsiveness but we could find a way to scissor the molecular structures and make then fuel responsive. When completely developed these systems will not only improve the fundamental understanding of non-equilibrium fueled assemblies but can potentially find numerous applications in different fields. We also developed another fuel responsive system which could create very sophisticated and complex microscopic assemblies forming hydrogels whose properties such as mechanical strength could be tuned very easily with respect to the composition of the ingredients and supplied fuel quantity. Such systems can also open door for potential application in optoelectronics or unique fuel modulated hydrogels with different compositions and strength for cell culture etc. The candidate during the period of the fellowship attended 2 conferences where the results were conveyed to a broad range of scientific community through interactive posters. The candidate also gave around 4 invited lectures in different universities from France, Spain and Germany which involved scientists and several aspiring students to inspire them towards this fast growing field of non-equilibrium supramolecular chemistry mimicking life like systems. The results were published in a very high impact respected journal which garnered lot of interest from both scientific and general public which was evident from the reception of the publication when posted on twitter and Facebook with a detailed explanation of the work through gifs and videos easily understandable to a wide range of audience. The publication reached over 2000 hits on the journal webpage and the twitter posts had more than 200 retweets and likes.

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)

The results of the project will be at the forefront of the non-equilibrium supramolecular chemistry field which will impact give great insights into how such persistent systems occurring in nature are both robust and sensitive to subtle signals at the same time. The ability of to control the lifetime and mechanical strength based on the fuel provided in the reaction cycle and further more in a continuously fueled reactor will allow not only to control the structure, length and radius of the microtubules mimicking nanotubes and hydrogels but also the emergent functions due to such wide range of achievable structures through the same mother material. More in general, the results from this action can go beyond the state-of the art in supramolecular chemistry, and therefore are expected to open the door to more life-like self-assembled materials with a whole range of new possible applications. Being able to create on
demand chemically fueled orthogonal systems with intricate architectures and ability to create and disassemble strongly assembling Nano tubular assemblies of cyclic peptides can find vivid application in several fields such as semiconductors, drug delivery, optoelectronics etc. The latter would strength the already well-recognized excellence of Europe in supramolecular chemistry, and project European research at the forefront of the promising field of non-equilibrium systems.

Biomimicking orthogonal assembly and selective response to fuel for targeted dissassembly