Designing minimal cells with 3D bioprinting

PhD student Hiromune Eto, Prof. Dr. Petra Schwille, and co-workers at the Max Planck Institute of Biochemistry managed to make cell structures change shape by 3D-printing proteins on the microscale. Hiromune Eto: “3D bioprinting gives us clues as to why cells or organelles are shaped the way they are.”

The ability of three-dimensional printers of biomaterials – 3D bioprinters – to mimic cells on the microscale makes this technique an attractive starting point for constructing minimal cells from the bottom up. Hiromune Eto makes use of a two-photon laser printer to create hydrogel protein structures. Since these bio-printed materials are proteins themselves, a specific 3D shape can trigger or enhance responses from the cell’s own proteins. Mr. Eto tells us more about his work with bioprinting, which was published in the journal Small.

How does 3D bioprinting work?

“By applying 3D-bioprinting to synthetic biology, we can print much more complex structures than has been possible before. Up until now, researchers have shaped biological material using two-dimensional fabrication methods, which limits what we can create. We could merely “pull up” 2D shapes, such as a circle or a square, and produce an “extruded” shape like a cylinder or a cuboid. Now, with 3D printing, our team can better mimic cellular features that are relevant to the proteins we study. This means we can influence different functions in the cell, like metabolism and the transport of materials.”

“We print structures or shapes in three dimensions on a microscopic scale or smaller, similar to the size of a cell. For this, we use a protein mixture of bovine serum albumin. We also work with polymer materials, which have many relevant and desirable biochemical properties. Biology, including cells and proteins, can interact with these 3D-printed biological materials in many ways. At the Schwille lab, we study two of those possibilities.”

How do the printed materials mimic cell functions?

“We can create different kinds of surface topographies through 3D printing that resemble cellular structures, for one. These geometrical features can in turn influence protein behavior. Our ability to build structures with a 3D printer is so precise, that we can now for example print a protein in a shape that makes it bind more strongly to another protein, triggering a different reaction inside the cell. This means we are able to link specific reactions inside a cell to a certain geometry, which gives us clues as to why cells or organelles are shaped the way they are.”

“The second technique has to do with directly 3D printing proteins in the form of hydrogel. The proteins react to the light from the laser: they crosslink to each other to form polymer networks or gels. We now have an exciting opportunity to 3D print micron-sized protein robots, with specific biochemical functionality. This is particularly cool because the things we print can directly interact with the cells that we study. They can also dynamically change shape – through changes in pH or through interactions with other proteins.”

What kind of applications are possible with 3D bioprinting?

Hiromune Eto in the lab with 3D printers

“The big advantage of 3D bioprinting is not that we can mass produce structures with one specific design, but rather that we can do rapid prototyping, where we can make many different designs relatively quickly. Micro-printing is particularly useful for working out what type of design is effective. It has already had a big impact on academic research as well as product development. Once we can confirm that a certain shape works, we can hand our proof of concept over to an industry partner who can place this design on the market.”

“The worldwide interest in the potential of 3D bio-printing is growing. Aside from our lab at the MPI, there are clusters in Japan, Singapore, the United States and Germany applying 3D printing to cells. A cluster of researchers in Switzerland for example is working on cell-made carriers – micro-swimmers – that can deliver drugs such as vaccines to specific parts of the body. Several groups in Heidelberg and Karlsruhe in Germany are also investigating how 3D printing can improve the regeneration of tissues. Researchers are even 3D printing artificial meat, meaning lab-grown meat, to revolutionize how food can be brought to our table.”

3D bioprinter at work: making the “cell” from BSA photoresin – image of the resulting printed cell can be found  in the article text above:

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Lab images and video: Hiromune Eto