ZEISS Axio Observer widefield microscope spinning on a centrifuge arm
DLR
Introduction

Live Cell Imaging Under Hypergravity: The DLR Hyperscope

High-end fluorescence microscope attached to a centrifuge analyzes cellular dynamics under increased gravity conditions

Neuronal activity affects cognition, learning, memory and motion. The reactivity of astrocytes is often targeted to promote neuronal regeneration and potentially reverse neurological disorders. Scientists at the Institute of Aerospace Medicine at the German Aerospace Center (DLR) are working to understand the impact of gravitational and mechanical loading on cells to potentially modify key features of astrocyte reactivity.

Dr. Christian Liemersdorf is a scientist at the Department of Gravitational Biology at the DLR in Cologne, Germany. He is researching the effects of altered gravity on the fundamental mechanisms regulating shape and mobility of cells in order to possibly employ novel therapeutic approaches against neurological disorders. To accomplish this, he uses an amazing set up, his live cell experiments are performed on a ZEISS Axio Observer live cell imaging microscope connected to a spinning centrifuge which generates hypergravity during data collection.

 

The Hyperscope was created by mounting a ZEISS Axio Observer live cell imaging microscope on the DLR Short Arm Human Centrifuge. This novel platform allows the study of cellular dynamics under increased mechanical loading in living cells and organisms using wide field transmitted light and fluorescence microscopy. Copyright: DLR

Creating the Hyperscope

The medical research facility, :envihab, at the DLR Institute of Aerospace Medicine, performs ground-breaking research into the ways people adjust to extreme environments and stressful situations, such as living in microgravity on the International Space Station (ISS). :envihab is home to the DLR Short Arm Human Centrifuge, which  is used to research the impact of increased gravity on humans and as a potential countermeasure against muscle and bone loss in space.

In order to allow microscopic observation of living cells under hypergravity, the DLR Short Arm Human Centrifuge was equipped with a ZEISS Axio Observer live cell imaging microscope to create the Hyperscope. This novel platform allows the study of cellular dynamics under increased mechanical loading in living cells and organisms.

  

Dr. Christian Liemersdorf

The Hyperscope is a novel system to directly image and analyze the effects of hypergravity on cells and tissues and to reveal yet unknown dynamics.

Dr. Christian Liemersdorf

Scientist, Department of Gravitational Biology, Institute of Aerospace Medicine, German Aerospace Center DLR, Cologne, Germany

Control HeLa cells stained with DAPI (blue) and anti-tubulin antibody (red) and imaged with ZEISS Celldiscoverer 7.
Control HeLa cells stained with DAPI (blue) and anti-tubulin antibody (red) and imaged with ZEISS Celldiscoverer 7.

ZEISS Axio Observer widefield microscope set up on a centrifuge for live cell imaging experiments under hypergravity. Copyright: DLR

ZEISS Axio Observer widefield microscope set up on a centrifuge for live cell imaging experiments under hypergravity. Copyright: DLR

Fully Automated Live Cell Imaging on a Centrifuge

To perform their experiments, Dr. Christian Liemersdorf and co-workers required hands-free high-end microscopy on live cells under increased gravitational (mechanical) stimulation.

The Hyperscope imaging system was designed to meet their needs. The image acquisition is controlled remotely during centrifuge operations and incubator parameters can be adjusted as needed. Fresh media or other substances can be perfused as desired. Centrifugation of the microscope can be carried out at a level of up to 4g for a duration of up to 24 hours.

The Hyperscope facility is available for cooperation with external partners and they encourage interested scientists to contact them.

  

Live Cell Imaging Examples

Acquired with the DLR Hyperscope

  • Live cell imaging applications performed with the Hyperscope: (1) Live scratch assay, (2) Intermittent gravity scratch assay, (3) Lamellipodium and retraction fiber dynamics, (4) Actin stress fiber stability, (5) Actin cortex and focal adhesion, (6) Membrane ruffling, (7) Astrocyte calcium waves. Copyright: DLR
LifeAct-GFP expressing astrocytes under 2g hypergravity imaged using ZEISS Axio Observer on the DLR Hyperscope.
LifeAct-GFP expressing astrocytes under 2g hypergravity imaged using ZEISS Axio Observer on the DLR Hyperscope.

LifeAct-GFP expressing astrocytes under 2g hypergravity imaged using ZEISS Axio Observer on the DLR Hyperscope. Copyright: DLR

LifeAct-GFP expressing astrocytes under 2g hypergravity imaged using ZEISS Axio Observer on the DLR Hyperscope. Copyright: DLR

Example Research

Astrocyte Physiology Under Hypergravity

One example of the work at the Department of Gravitational Biology at the DLR can be found in Lichterfeld et al. (2022). They report that hypergravity attenuates the reactivity of primary murine astrocytes with regards to cell shape, behavior and protein and gene expression. Normal astrocytes maintain CNS tissue homeostasis, but reactive phenotypes may go along with neurodegenerative diseases. Reactive astrocytes have beneficial functions during acute phases following neuronal injury, but later they show detrimental effects by effectively inhibiting neuronal regeneration. Dr. Liemersdorf and colleagues discovered that hypergravity did not induce a reactive phenotype, and were even was able to inhibit certain aspects of astrocyte reactivity.

New therapies of neuronal disorders, based on alterations induced by a moderate stimulus such as increased gravity, may promise an enormous potential to treat patients worldwide.

Dr. Christian Liemersdorf

Department of Gravitational Biology, Institute of Aerospace Medicine, German Aerospace Center DLR, Cologne, Germany


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