Periodic Reporting for period 1 - PHOTOMECH (Photomechanical writing of cell functions)
Período documentado: 2021-05-01 hasta 2022-10-31
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.
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.
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 the preliminary experiments 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 (see JoVE paper), thus having major input for the characterisation of cellular forces. In addition, as we finally want to establish photoswitchable 3D printed materials, we have set up a 3D laser printing system and have already managed to print and characterise the printed structures. We have also designed the optical setup and can now proceed with ordering all devices. This work has been strongly delayed (see risks part), as the postdoc who I wanted to hire for 1.1.22 could not leave China for a long time and neither got a visa during that time, as the German embassies there were closed.
The activities we have carried out furthermore were participations in a project retreat (Dec 13-14, 2021), organising conference (MSEB in Heidelberg, 19-21, Oct, 2022; Mechannobiology in Evolution, July 4-6, 2022) and also participating in the Girls days reguarly (2021, 2022). The group members also participated in conferences. We are also actively including students into the project.
The activities we have carried out furthermore were participations in a project retreat (Dec 13-14, 2021), organising conference (MSEB in Heidelberg, 19-21, Oct, 2022; Mechannobiology in Evolution, July 4-6, 2022) and also participating in the Girls days reguarly (2021, 2022). The group members also participated in conferences. We are also actively including students into the project.
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 frequency, duration, history, and intensity of the 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. Therefore we are already strongly follow activities of colleagues in the field of living materials, in order to be able to contribute once our setups and our data are significantly solid.
Due to our advanced already in the first part of the project (in spite of all pandemic delays) we are very optimistic that we will achieve our goals of the project.
Due to our advanced already in the first part of the project (in spite of all pandemic delays) we are very optimistic that we will achieve our goals of the project.