MagMech: Precision magnetic tweezers for the mechanobiology of cells and tissues.

Project Information

MagMech

Grant agreement ID: 101069173

DOI

10.3030/101069173

Project closed

EC signature date 31 March 2022

Start date 1 September 2022

End date 29 February 2024

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 1 - MagMech (MagMech: Precision magnetic tweezers for the mechanobiology of cells and tissues.)

Reporting period: 2022-09-01 to 2024-02-29

Summary of the context and overall objectives of the project

Mechanobiology is an emerging cross-disciplinary field that studies the contribution of physical forces within and around cells or tissues. One indispensable element for this field and its application to health care and diagnosis is the development of accurate methods and devices to apply and measure mechanical forces to live cells and tissues, and intracellular organelles. As of now, the only commercial solutions include Atomic Force Microscopy and Optical Tweezers systems, which are limited in term of application. Notably, the market does not propose devices to probe forces in large multi-cellular tissues like embryos and tissue explants down to intracellular organelles, such as the nucleus.
The MagMech project proposes an innovative method, initially developed in the context of the ERC CoG project “FORCASTER” based on the development of a robust Magnetic tweezer methodology that allows to apply and measure forces on magnetic particles addressed to the surface or within a range of live cells and tissues. The specific work packages and goals of the project are: WP1: To improve several technological developments of the magnetic tweezer device, in order to enhance robustness, versatility, ease of use and reproducibility. WP2: To validate the device in a set of relevant of biological systems, including tissues and in vitro situations. WP3: To define several prototype magnetic kits, and share them with partners both in industry and academia to evaluate the potential of the method for commercialization. WP4. To expand the intellectual property and evaluate the market potential of the device.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Related to WP1, we have devised several kinds of new magnets, by improving magnet tip designs, in order to generate a range of devices that can be used for various range of force application. In addition, we implemented a systematic experimental protocol and home-made image analysis pipeline to calibrate the magnetic force. The experimental assay is based on tracking the velocity of magnetic beads in test viscous solution (Glycerol 80%), as a function of their size and distance to the magnet tip. Related to WP2, we performed novel assays to use the device to other biological contexts. Notably we: (i) performed experiments in drosophila embryo (collaboration with Y. Bellaïche), and demonstrated that the device can be used to manipulate spindle position in large developing embryos, as well as apply forces on intercellular junctions in order to minor their mechanical properties, as well as assays mechanosensing pathways at junctions. (ii) We used the device to perform a systematic mapping of viscoelastic properties of bulk cytoplasm during the development of sea urchin embryos. (iii) Implemented a novel assay based on the use of water in oil droplets that encapsulate cytoplasm extracts and large magnetic probe to preform rheological measurements in a medium-throughput manner in different kind of cytoplasm extracts. Importantly throughout these novel assays in different living multicellular systems and in vitro, we improved methods for injecting and coating magnetic probes, which also helps contribute to the execution of WP1 and WP3. As a continuation of the project, we are currently collaborating with 2 other groups to implement and test the device in the context of multicellular intestinal organoids (Collaboration, D. Delacour, IBDM, Marseille, France) and the regeneration of heart tissues in zebrafish embryos (Collaboration with Kimara Targoff, Columbia University, NY, USA). Related to WP3, we have initiated to define the content of kits with out TTO partner CNRS innovation. The kits shall be ready to be shared in the next coming months, as the material is readily available. Related to WP4, our TTO partner CNRS innovation has (i) conducted an anylsis of the technology with respect to the state of the art, (ii) perfomed an interview of KOLs; (iii) expanded the IP by filing european and US extension of the patent and (iv) initiated discussions with our prefered industrial partner Impetux.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The results produced in the MagMech project have already impacted academic and industrial research through (i) the publication of an international patent in 2024 (Minc et al, US Patent App. 18/032,817/ Filing date 04/20/2023; EP4232817 / Filing date 05/22/2023); ‘ii) the publication of a review article led by the post-doc hired on the project summarizing important technological developments for mechanobiology including our magmech method (Arjona et al, 2023) and iii) presentation of the device and some of its application at several international conferences by Maria Isabel Arjona (CELLMech2023. Marseille, France. September, 2023; Physics of living systems: From physical principles to biological function. Dresden, Germany. July, 2023) and by Nicolas Minc (Mecanobionic, 2024, Nice, France; Forces across scales, Porto, Portugal, 2024).

As mentioned above, we are currently discussing and negotiating with one potential industrial Partner (Impetux, Barcelona, Spain), and the “magnetic kits” for evaluating the potential for commercialization, are being finalized. In addition, the validation and licensing of the patent will only occur in the next few months.

Overall, the Magmech project allowed us to improve multiple technological aspects of the device, as well as progress significantly towards the future commercialization of the device.