12. May 2022

Cells in 4.7 seconds of zero gravity Cells in 4.7 seconds of zero gravity

In a unique joint project, doctoral students from the University of Bonn, DLR Institute of Aerospace Medicine and TH Köln have investigated neuronal networks at the ZARM drop tower in Bremen.

Mechanical humming and a loud hissing noise are audible in the circular room with orange-colored metal walls. A group of young researchers carrying a transport container the size of a picnic cooler stand in front of a cylindrical capsule. Whilst the majority of the figures are concentrating on their load, one of their number is looking upwards. Following his gaze, the viewer becomes aware of the tall tubular nature of the room; stairs lead a little way upwards until the view narrows and occludes. Pumping noises and a long drawn-out squeal at rhythmic intervals of a few seconds lend further tension to the atmosphere.

A multi-storey apparatus houses the experimental objects and the the test objects and the necessary measuring instruments
A multi-storey apparatus houses the experimental objects and the the test objects and the necessary measuring instruments - . The entire setup is packaged in a pressure-tight drop capsule - 2.5 meters long and 80 centimeters wide. The capsule is pulled up a 120 meter high tube. © Gregor Hübl / Universität Bonn
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Doctoral student Johannes Striebel carefully takes a small bowl from the transport container. The bowl contains the main protagonists of this curious undertaking—a pink mass of live nerve cells forming connections with each other—which are placed on an electronic chip. He and his colleagues fix the bowl on a measuring plate. Many hands help with the screwing until all the wires, hoses and meters are in place. Two helpers stow the multi-story equipment under an elongated, spherical-looking metal capsule. Cables begin to pull the capsule up a 120-meter high tube. It’s just before 4pm and the moment everyone has been working towards all day: the drop.

The drop is what the researchers call an experiment in the Bremen drop tower ZARM. Experimental objects are dropped from more than a hundred meters down an air-free pipe. Conditions of zero gravity develop for 4.74 seconds. Research teams from all over the world come to the facility in Bremen to conduct a range of experiments under these special conditions.

Doctoral student Johannes Striebel from the University Eye Hospital in Bonn and his colleagues from TH Köln and the DLR Institute of Aerospace Medicine in Cologne are now among them: Their joint project “MIND Gravity” was selected for the European Space Agency “Drop your Thesis” funding program. Johannes Striebel, Kendrick Solano, Laura Kalinski, Yannick Lichterfeld, Stefan Lukas Peters and Nils Drouvé are now spending two weeks at the Drop Tower in Bremen to research the neuronal impact of zero-gravity.

“The whole atmosphere reminds you of a NASA project,” says Johannes Striebel as he and the team walk through the hall built around the drop tower to the control room. Indeed, visitors to the facility are immersed in a world usually known only from television or the Internet.
A large monitor in the darkened room—which could easily be located in a space center in the USA—displays the recordings from different cameras trained on the various stations within the drop tower up to its highest point at 120 meters. Mechanical arms have received the capsule and are waiting for the signal to send it into free fall.

The scientists take their seats in the control room. Whilst some scrutinize the screens or their checklist, others carry out final measurements on the sensitive cells from a distance and confer quietly. If the experiment is unsuccessful, their efforts of the day have been wasted, because the schedule is strict and the complicated action cannot be repeated endlessly. After about ten minutes and a final check, the team triggers the fall with a decisive push of a button; the monitor shows the mechanical arms releasing the capsule. After 4.7 seconds of silence, the capsule appears in another monitor and lands in the catch tank. Relieved applause fills the room followed by the question: Have the cells survived? Returning their gaze to their laptops, everyone is relieved to learn that the cells are sending action potentials, i.e. nerve impulses that transmit stimuli, showing that they are active. “It is almost unbelievable that the networks are still working after the fall, because the cells hit at an acceleration force of 30 to 50 g,” explains Laura Kalinski.

The early-career researchers spent a year preparing for this experiment. They were the first to explore how a network of neuronal cells reacts under the influence of zero-gravity. This experiment was previously only conducted on single cells. The group conducted their experiment using new Multi-Electrode Array (MEA) technology, which enables them to cultivate entire networks of around 100,000 cells on tiny electrodes and thus observe the complex signals exchanged between the neuronal cells in real time. Since these signal processes happen within milliseconds, the 4.7 seconds of weightlessness are sufficient to detect changes in activity.

The team’s primary aim is to establish the influence of gravity changes on the electrical activity of neurons and whether it is possible to change the results through pharmacological intervention. To this end, they applied hydroxynorketamine—an intermediate product of ketamine used in the treatment of depression—to half of the cell cultures. Teamwork is important: Chemists from TH Köln are responsible for producing and analyzing the substances, while neuroscientists from the Bonn Eye Hospital and the DLR Institute of Aerospace Medicine are charged with cultivating the neuronal cells on the MEA system. Operation of the complex hardware is primarily the responsibility of DLR staff.

Background: Hydroxynorketamine is a metabolite of the well-known drug ketamine, which is used primarily as a narcotic, but also to treat depression.

Back in the drop tower, the experiment has left its mark: small polystyrene balls have spread across the concrete floor and crunch underfoot. Coming from the eight-meter deep catch tank, they are used to cushion to fall. The ZARM staff use a strong jet of air to clean the capsule of any remaining polystyrene. For the team members, it’s all about returning their most valuable asset, the cells, back to the transport container. The container has been adapted perfectly to ensure that the needs of the cells—exactly 37 degrees Centigrade and a CO2 value of five percent—which means that they continue to thrive and their pH-value does not change.

A sound like something out of a science fiction movie travels through the hall - high and shrill, as if air were escaping from a giant bottle, followed by a loud bang, like an impact on metal. After almost two weeks of work on the drop tower, the sound no longer elicits a blink of an eye from the young researchers. This is the sound of air receding into a pumped-out tube of this size.

Johannes Striebel and Laura Kalinski take the cells back to the biology lab, a few hundred meters from the tower, where they look at the neuronal networks under the microscope and compare the images with those recorded before the experiment.

The rest of the team is already back at the workstation in the light-flooded hall right next to the drop tower. “We think of an improvement every day”, says engineer Stefan Peters, typing something into his laptop on a long table next to cables, tools and notes. These are long days for him and his colleagues. The following months will be filled with measurements. No one can say what they will find. “But then that is why we do science”, concludes Johannes Striebel.

The control room from which the team controls  and observes the case of their experiment
The control room from which the team controls and observes the case of their experiment © Gregor Hübl / Universität Bonn
At the top of the tower: the capsule before the fall
At the top of the tower: the capsule before the fall © Gregor Hübl / Universität Bonn
Networks of more than 100,000 cells are cultivated on tiny electrodes on a chip.
Networks of more than 100,000 cells are cultivated on tiny electrodes on a chip. - The method is called microelectrode array technology and makes it possible to observe the complex signaling processes of the neuronal cells in real time. The neurons are derived from stem cells, which in turn were developed from human skin cells. © Gregor Hübl / University of Bonn
Preparing the drop: cautiously, the team takes the cell cultures out of the transport box ...
Preparing the drop: cautiously, the team takes the cell cultures out of the transport box ... © Gregor Hübl / University of Bonn
Under the microscope: signal measurement of neuronal networks in the biology laboratory
Under the microscope: signal measurement of neuronal networks in the biology laboratory © Gregor Hübl / University of Bonn
Laura Kalinski and Johannes Striebel at the experimental setup
Laura Kalinski and Johannes Striebel at the experimental setup © Gregor Hübl / University of Bonn
…and attaches it on a measuring plate.
…and attaches it on a measuring plate. © Gregor Hübl / University of Bonn
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