Photomechanical writing of cell functions

Project Information

PHOTOMECH

Grant agreement ID: 101001797

DOI

10.3030/101001797

EC signature date 23 February 2021

Start date 1 May 2021

End date 31 October 2027

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 433 445,00

EU contribution

€ 2 433 445,00

Coordinated by

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Germany

Periodic Reporting for period 3 - PHOTOMECH (Photomechanical writing of cell functions)

Reporting period: 2024-05-01 to 2025-10-31

Summary of the context and overall objectives of the project

Generating artificial organs and tissues from stem cells would revolutionize regenerative medicine and open the door to controllable, biology-based robotics. These systems require a physical understanding of cells, specifically their dynamic and adaptive responses to external forces. This “mechanotransduction” is already known to control important cellular functions, and even stem cell differentiation. With the project proposed here, we plan to bring our quantitative understanding of
force-controlled cell functions to a new level by a challenging and novel photomechanical cell stimulation approach. It combines new materials containing photoswitchable molecules with a complex optical system employing intense laser light pulses. The project can lead to a paradigm-shift in many fields, from biophysics to regenerative medicine, synthetic biology and biohybrid robotics.

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

We have checked topic-related literature and have designed the possible synthetic route for photoswitchable azobenzenes. We have already synthesized two different azobenzenes with optimized conditions and overcome the difficulties in their purification. Furthermore, the synthesized azobenzenes could be triggered by UV and NIR light and present low rate of thermally induced relaxation. We have established a process for the surface functionalization of glass slides with azobenzene compound and the photo-isomerization process was successfully characterized. Furthermore, cell adhesion was observed on the azobenzene-functionalized surface in theexperiments and also single-cell force microscopy experiments are promising, confirming a switching of cell adhesion by the novel materials generated. Furthermore, we have advanced the single-cell force microscopy setup by including novel algorithms and also by establishing a novel method for characterising the impact of cell contact area in relation to measured forces by using microstructures. This will significantly improve the reliability of the measurements in this project. We have also explored already several methods to measure cellular forces. We have set up the laser system and are currently calibrating it. We have highly interesting results on the stimulation of stem cell differentiation by the azoebnezes.

The activities we have carried out furthermore were participations in a project retreat, organising conferences and also participating in the Girls days regularly. The group members also participated in conferences. We are also actively including students into the project. We are also active in dissemination to the public and in touch with politicians. We are considering applying for an ERC PoC grant.

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)

We expect to bring our quantitative understanding of force-controlled cell functions to a new level by a challenging and novel photomechanical cell stimulation approach. It will combine new materials containing photoswitchable molecules with a complex optical system employing intense laser light pulses. By pulsing the laser, we can apply controllable force stimuli on cells through a conformational change of the photoswitchable molecules. We expect that cell functions, such as adhesion, migration and differentiation, have a huge systematic dependency on the physical properties of force stimuli. With this strategy for photomechanical stimulation of cellular proteins, we will be able to collect previously unobtainable physical information within cells on multiple size scales, from the single molecule to tissue level. Using the laser like a pen, we will be able for the first time to write cell functions in 3D, imitating the growth of the cellular scaffolds in living creatures: a completely new means of photomechanically controlling multicellular structures. Ultimately, the tools and materials we study in this interdisciplinary project will allow for the writing of multicellular structures in vitro and in vivo by force-induced mechanotransduction in stem cells. It will lead to a paradigm-shift in many fields, from biophysics to regenerative medicine, synthetic biology and biohybrid robotics.

Sketch of a cell on a functionalized, photoresponsive surface