Another step towards synthetic cells

Another step towards synthetic cells

DNA-based imitations of cytoskeletal filaments for reversible assembly and transport of goods. Credit: University of Stuttgart and Max Planck Institute for Medical Research

Building functional synthetic cells from the bottom up is a constant effort of scientists around the world. Their use in the study of cellular mechanisms in a highly controlled and predefined environment creates great value for the understanding of nature, as well as for the development of new therapeutic approaches. Scientists from the Second Institute of Physics at the University of Stuttgart and colleagues from the Max Planck Institute for Medical Research have already managed to take the next step towards synthetic cells.

They introduced functional DNA-based cytoskeletons into cell-sized compartments. Cytoskeletons are the main components of each cell that control their shape, internal organization and other vital functions, such as transport of molecules between different parts of the cell. Following the incorporation of cytoskeletons into synthetic droplets, the researchers also demonstrated functionality, including transporting molecules or assembling and disassembling certain triggers. The results were recently published in Chemistry of nature.

A challenge to mimic cytoskeletal function

The cytoskeleton is an important component of every cell and consists of various proteins. In addition to the basic function of shaping the cell, it is essential for many cellular processes such as cell division, intracellular transport of various molecules and mobility in response to external signaling. Due to its importance in natural systems, the ability to mimic its functionality in an artificial setting is an important step towards building and designing a synthetic cell. However, it comes with many challenges due to its diverse requirements, including stability, as well as rapid adaptability and responsiveness to triggers.

Researchers in the field of synthetic biology have previously used DNA nanotechnology to recreate cellular components such as DNA-based imitations of ion channels or cell linkers. Therefore, they take advantage of the fact that DNA can be programmed or designed to self-assemble in a pre-planned form by complementary base pairing.

Another step towards synthetic cells

Transport of vesicles by DNA-based imitations of cytoskeletal filaments in a closed space the size of a cell. Credit: University of Stuttgart and Max Planck Institute for Medical Research

DNA filaments as a synthetic cytoskeleton

“Synthetic DNA structures can allow for very specific and programmed tasks, as well as multifaceted design possibilities beyond what is available from biologically defined instruments. In particular, the structural organization of DNA structures may deviate from their natural counterparts, even likely to overtake the functional range of natural systems, “said Laura Na Liu, a professor at the 2nd Institute of Physics, University of Stuttgart.

In addition, researchers Paul Rothemund, Eliza Franco and Rebecca Schulman have already managed to assemble DNA into micron strands that form the basis for building a cytoskeleton. Since then, these threads have been equipped with various functions, such as assembly and disassembly under external stimulation or inside a compartment. Scientists from the University of Stuttgart and the MPI for Medical Research have now taken the next step in building an artificial cell, using the fibers as a synthetic cytoskeleton and providing them with a variety of functionality.

“It’s exciting that we can also trigger the assembly of cytoskeletal DNA with ATP, the same molecule that cells use to power various mechanisms,” said Kerstin Gopfrich, head of Max Planck’s research team at MPI Medical Research.

Accelerate the transport of vesicles

Moreover, the team of scientists managed to provoke the transport of vesicles along the fibers using the burnt bridge mechanism introduced by Khalid Salaita. This mimics the transport of vesicles in parts of the natural cytoskeleton in cells called microtubules. “Compared to transport in living cells, transport of our DNA filaments is still slow. Accelerating it will be a challenge for the future,” said Kevin Janke, first author and postdoc in Kerstin Gopfrich’s group at MPIMR.

Pengfei Zhan, a postdoc in the group led by Prof. Laura Na Liu from Stuttgart, added: “It was also a challenge to refine the energy landscapes of the possibilities for assembling and disassembling the strands of DNA nanostructure. In the future, the functionalization of DNA filaments will be even more crucial to mimic natural cells even better. In this way, researchers could create synthetic cells to learn cellular mechanisms in more detail or developing new therapeutic approaches.

The study shows that the cytoskeleton of the cell does more than hold the cell, it carries energy

More info:
Pengfei Zhan et al, Functional DNA-based cytoskeletons for synthetic cells, Chemistry of nature (2022). DOI: 10.1038 / s41557-022-00945-w

Quote: Another step towards synthetic cells (2022, June 21), retrieved on June 21, 2022 from

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