Cells On the Rack

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Electron micrograph of the ’empty’ scaffold (without hydrogel) that
Electron micrograph of the ’empty’ scaffold (without hydrogel) that an international research team used to deform individual cells. | © Marc Hippler, KIT

Device the size of a few micrometres provides insight into how cells respond to mechanical stress

Cell behaviour - for instance during wound healing - is controlled by biological factors and chemical substances, with physical forces such as pressure or tension also playing a role. As part of the research carried out at the joint Cluster of Excellence "3D Matter Made to Order" (3DMM2O), researchers from Karlsruhe Institute of Technology (KIT) and Heidelberg University developed a small stretching rack the size of a few micrometres which allows them to analyse the influence external forces exert on individual cells. Using 3D printing, they created micro-scaffolds with four pillars each on top of which a cell settles. Triggered by an external signal, these pillars are pushed apart and the cell is forced to "stretch".

To produce their cell "racks" the researchers used "direct laser writing", a special 3D printing technique where a computer-controlled laser beam is focussed on a special liquid ink. The ink molecules only react in the exposed areas, forming a solid material. All other areas remain liquid and can be washed away. As a result, three-dimensional structures can be built on the micrometre scale and below.

Here, the researchers used three different types of ink. The first ink, made of protein-repellent material, was used to form the actual micro-scaffold. Using a second ink consisting of protein-attracting material, the researchers then created four bars, each of which connects to one of the pillars. The cell attaches to these four bars. A third ink served to "print" a mass inside the scaffold. This hydrogel mass expands when a special liquid is added, developing enough force to move both the pillars and the bars and thus to stretch the cell.

Two very different types of cells where placed on this micro rack: human bone tumour cells and embryonic mouse cells. The researchers found that the cells counteract the external forces with motor proteins and thus greatly increase their tensile forces. When the external stretching force is removed, the cells relax and return to their original state, demonstrating their ability to adapt to a dynamic environment. As the researchers explain, if the cells were unable to recover they would no longer be able to fulfil their purpose, which includes closing wounds, for instance.

This research at the Cluster of Excellence was performed by biophysical chemists from Heidelberg under the direction of Motomu Tanaka as well as physics and celland neurobiology researchers from Karlsruhe. Also involved, alongside Australian experts, were researchers from the German-Japanese University Network HeKKSaGOn.

At the Cluster of Excellence "3D Matter Made to Order", scientists based at the Karlsruhe Institute of Technology and at Heidelberg University conduct interdisciplinary research into innovative technologies and materials for digital scalable additive manufacturing to enhance the precision, speed, and performance of 3D printing. The aim is to completely digitalise 3D manufacturing and materials processing from molecule through to microstructure. In addition to being funded as a Cluster of Excellence under the Excellence Strategy competition of the federal and state governments, 3DMM2O is supported by the Carl Zeiss Foundation.

M. Hippler, K. Weißenbruch, K. Richler, E. D. Lemma, M. Nakahata, B. Richter, C. Barner-Kowollik, Y. Takashima, A. Harada, E. Blasco, M. Wegener, M. Tanaka, M. Bastmeyer: Mechanical Stimulation of Single Cells by Reversible Host-Guest Interactions in 3D Micro-Scaffolds, Science Advances, 2020,