01 December 2021

The third generation of xenobots

Pacmans from frog stem cells were able to self-copy

Alexander Dubov, N+1

American biologists have collected clusters from frog stem cells that are capable of almost endless self-copying. A cluster in the shape of a spheroid with a cut (it looks like a Pacman) rakes single stem cells into a new cluster of the same shape, which in five days can also begin to collect its own copies from individual cells. Previously, such a method of self-replication and self-organization in cellular systems was not observed, scientists write in the Proceedings of the National Academy of Sciences (Kriegman et al., Kinematic self-replication in reconfigurable organizations).

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Drawings from the article by Kriegman et al.

The ability to reproduce itself is one of the key properties of any living system. The processes of creating copies (or analogues) of an entire organism, a single cell, or even a molecule are necessary for the survival of a species or individual. At the level of organisms and cells, the principle of self—reproduction is the cultivation of a similar system under the control of the parent organism, while the stages of development of the daughter organism are honed during evolution. Self-reproduction at the level of individual molecules occurs differently: it is a complete copy of the chemical and spatial structure. Copying is a much faster and more flexible process, and it is relatively easy to carry out it for individual molecules of molecules, but it is not observed in nature at the level of complex cellular structures. 

American biologists led by Josh Bongard from Tufts University have discovered that cell clusters can also produce their own copies by simply assembling individual cells into a similar structure. To show the realism of this method, scientists used stem cells from the blastula of a smooth spur frog (Xenopus laevis). If we take stem cells from the animal pole of the embryo, then in a salty aqueous solution at a temperature of 14 degrees Celsius, they naturally develop into spheroid clusters of about three thousand cells in five days. Inside these clusters are the cells of the epidermis, and on the surface are the cells of the ciliated epithelium, thanks to which the cluster can actively move.

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Movement of spheroid clusters in a medium of single frog stem cells

Scientists have found that if these cellular spheroids fall into an environment in which there are many single stem cells, then actively moving in it, clusters can "rake" individual cells into new clusters of the second generation, which after five days grow to spheroids with a similar structure.

If the second-generation cell clusters are separated from the parent clusters and also placed in an environment with a large number of single stem cells, then they similarly collect these cells into new clusters due to random active movement. However, after one or two generations, the ability to self—copy is lost - either due to a violation of the form, or due to a change in the trajectories of movement.

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The cycle of self-reproduction of spheroid cell clusters. The daughter generation of spheroids is extracted, matures and placed in a medium from single stem cells, where self-copying continues

To increase the number of generations after which cell clusters lose the ability to create their own copies, scientists used computer modeling. It turned out that for reproducibility, it is enough to slightly modify the shape of the cluster by making depressions or holes in the spheroid. Having tested many different possible forms using an evolutionary algorithm describing two-dimensional arrays of particles, scientists have found a form that allows self-copying almost indefinitely. A cluster resembling a Pacman in shape rakes cells into similar structures, which then after five days can do the same.

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A model of the movement of spheroidal clusters with a section in a medium of single stem cells

The scientists note that the self—copying mechanism they proposed does not require any genetic modification and additional control of chemical interactions - it is a purely kinematic mechanism in clusters of ordinary stem cells. Due to this, it is possible to copy clusters with a very wide spread in size. According to the researchers, the results of their work allow us to better understand under what conditions self-reproduction is generally possible in living organisms, and may also be useful for creating similar artificial systems.

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