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Unscrambled Eggs

This is a rather eerie result. Two researchers at Stanford report that the often-used model system of Xenopus frog eggs have self-organizing properties. Extracts from homogenized eggs had already been known to be more functional than one might have predicted (the paper has a number of references to such studies), but this paper finds that homogenate from such eggs, if left standing, organizes itself into compartments within about half an hour (see at right). These things are 300 to 400 microns across, and their formation require ATP and involves microtubule polymerization. There doesn’t seem to be a propagation wave moving across the samples; it happens across a large field more or less simultaneously. And this takes place in the presence of cycloheximide (which inhibits protein translation), so it doesn’t seem to be the result of some new program being initiated.

Nuclei, mitrochondria, microtubules, endoplasmic reticulum and other components end up distributed through these compartments in ways that are quite similar to the original cells – for example, there’s a single nucleus or cluster of nuclei found in the center. The clear borders between each of these seem to be “organelle-depleted” cytoplasm. The authors verified that this organization took place in both the presence and absence of frog sperm (which naturally set off profound cytoplasmic changes when combined). It’s faster with added sperm, but happens regardless. The effect needs a certain concentration threshold – diluting the homogenate slowed or abolished it.

Now, these were all interphase-arrested cells. But the paper goes on to use homogenates that are capable of going through the cell cycle (no cycloheximide in there, for one thing). These formed the same sorts of compartments, and adding demembranated sperm nuclei to this mixture caused the compartments to divide as if they were normal egg cells. Each of the new smaller compartments had a similar division of organelles as the “parent”, and in many cases the process ran further, with these dividing in turn.

So it appears that the cell contents, when totally mixed, are able to roughly reconstitute themselves into units that are about the size of cells, contain the appropriate subcellular fractions, and can go through some of the most important cellular processes. Now, these things are surely deficient in many ways; I would not recommend homogenizing your body’s own cells to get a fresh start for the new year. But it’s remarkable that this level of order can be regained. The “moving parts” of the cell fit together more robustly than one might have imagined. Are these compartments alive? What exactly does “alive” mean?

 

29 comments on “Unscrambled Eggs”

  1. Nate says:

    This put me in mind of an article I found fascinating in a similar vein – “How to uncook egg whites”

    Shear-Stress-Mediated Refolding of Proteins from Aggregates and Inclusion Bodies, Yuan et al, DOI: 10.1002/cbic.201402427

  2. Josh says:

    I felt deja vu reading this. Then I realized that I read about this on Quanta magazine, which reported it on January 2. It made no mention of homogenizing your body’s own cells to get a fresh start for the new year.

    https://www.quantamagazine.org/unscrambled-eggs-self-organization-restores-cells-order-20200102/

    1. Derek Lowe says:

      Well, see, that’s the kind of quality additional content that you get around here. . .

  3. James C. says:

    Congratulations are in order for that excellent title.

    1. MechChemPoly says:

      Don’t you mean egg-cellent?

  4. Brett Alcott says:

    Paging John Carpenter…

  5. Barry says:

    Self-organization–although not predictable–does make the emergence of life less improbable. We’re pretty solid on the structure of atoms and of covalent molecules. But inter-molecular forces are still not well treated.

  6. Ron Richardson says:

    In 1996 Julie Theriot wrote a brief piece entitled “The Importance of being random, which included the paragraph: “Living systems are always in a state very far from chemical equilibrium, but not all non-equilibrium states are equally likely, and very few of them are conducive to the perpetuation of life. How particular non-equilibrium states are assiduously pursued by every cell, and how every cell maintains its profound metastability and remains poised to follow an effectively infinite variety of behaviors, remain fundamental mysteries. Cells do not disobey the laws of thermodynamics, but rather hydrolyze enormous quantities of ATP in a highly directed way in order to defy them. Thus, we can expect that one particularly important principle in cell biology will be defined when my question for Wolpert’s “good fairy godmother of science” has been answered: how exactly does the cell trade off energy consumption against the normal effects of entropy, so that it can exploit random events in such a way as to yield consistent, predictable behavior? Once we know this, we may begin to answer arguably the most fundamental question in biology: what exactly is the difference between living and non-living chemical systems?”

    1. TruthOrTruth says:

      Thank you for that reference. Excited to read this essay!

  7. Tran Script says:

    Is this the dawn of a new area of study: cell folding?

  8. mymagoogle says:

    Well, I will be the snarky one and wonder out loud how soon the first biotech commercializing whatever is going on here for human use will get VC funding.

    1. loupgarous says:

      I’m sure someone will have a presentation for the 2021 J.P. Morgan shindig (sounds like something Alexis Borisy will have ready for VCs long before then).

  9. Anonymous says:

    I was borderline tempted to post a reference to Gilbert Ling and his Association Induction Hypothesis on the “Inside the Lipid Droplets” topic a few days ago (16 January, 2020) but this is an ever better place. From the Ling wikipedia page (link in my handle), “the Association Induction Hypothesis is a claim related to the properties and activities of microscopic assemblies of molecules, atoms, ions and electrons of the smallest unit of life called nano-protoplasm.” (And see refs 24 and 25, therein, free PDFs of two of Ling’s works.)

    One simplification of Ling’s AIH could be “Life without cell membranes.” He was considered a bit of a kook. I hope that others can improve on the tie-in.

  10. Sara says:

    That’s egg-citing!

  11. bks says:

    Amoeba can carry on without a nucleus. Click handle for sample article.

    1. for a short while (as can red blood cells)

      1. Andre Brandli says:

        Good point, Mike. Red blood cells (in mammals) survive for 100-120 days without nuclei. In fish and amphibia, red blood cells remain nucleated after maturation.

  12. Chacao says:

    Does this help to explain The Terminator 2?

  13. JS Rosenblum says:

    I don’t find this surprising at all. During my postdoc in the late 1990s, all sorts of studies came out about simple ways to turn xenopus extracts into more organized environments. The unifying element that I remember from those days was the GTPase Ran. For example:
    Self-Organization of Microtubule Asters Induced in Xenopus Egg Extracts by GTP-Bound Ran

    T. Ohba, M. Nakamura, H. Nishitani, T. Nishimoto*
    See all authors and affiliations
    Science 21 May 1999:
    Vol. 284, Issue 5418, pp. 1356-1358
    DOI: 10.1126/science.284.5418.1356

  14. Anon says:

    “homogenizing your body’s own cells to get a fresh start for the new year.”

    Cue the next BBC headline…

  15. Chris Phoenix says:

    As soon as the salamander heart is cut open, blood pools around the wound and clots quickly, usually in about one minute, sealing the hole like wet plaster. Almost immediately, the nearest red blood cells crack open like eggs. Their nuclei, surrounded by a thin coating of cytoplasm, glide by some means yet unknown directly to the raw, frayed edge of the heart muscle and insinuate themselves into the tangle of dying and injured cells. To a biologist this sight is bizarre, uncanny. It’s as though the engine of a passing car could walk up to a stranded truck, climb under the hood, and drive it away.
    Farther away from the wound surface, the red cells also spill out their nuclei, but these cell yolks clump together, fusing their remaining cytoplasm to form a syncytium. Still farther away from the center of action, the red cells undergo the more leisurely dedifferentiation we observed in our frog fractures and DC culture studies. They turn into primitive ameboid cells that move toward the area of damage and attach themselves by pseudopods to the injured muscle fibers. [….]
    All these changes are well under way within fifteen minutes. Soon afterward the extruded nuclei, the interconnected syncytial nuclei, and the ameboid cells are all dividing as fast as they can building up the blastema. It’s fully formed within three hours after the injury. By then its cells have already started to redifferentiate into new heart-muscle cells, synthesizing their orderly arrays of contractile fibers and connecting up with the intact tissue. If the clot contained more blood cells than were needed, the extras outside of the area now degenerate, apparently so as not to get in the way of the repair work.
    Meanwhile, the newt has survived by absorbing dissolved oxygen from the water through its skin. Now, at about the four-hour mark, there are enough new muscle cells to withstand contraction [….] after a day [the heart is] indistinguishable from an uninjured one.

    From The Body Electric by Robert O. Becker, M.D. and Gery Selden (1985), pp. 198-200

    1. PUI Prof says:

      In what organism do red bllood cells have nuclei???

      1. loupgarous says:

        Enucleated RBCs are a mammalian evolutionary development, according to wikipedia’s article “Red blood cell” . Only two non-mammalian vertebrate groups don’t have nuclei: “salamanders of the genus Batrachoseps and fish of the genus Maurolicus.” (quoting the wikipedia article).

  16. Chris Phoenix says:

    In his book The Body Electric (1985), Robert Sheldon reports that newts can survive having half their heart cut away. They absorb oxygen through their skins for the four hours it takes for the red cells in the clot to split open and reorganize their contents into heart muscle cells. The nuclei of the red cells closest to the cut muscle edges actually migrate into the injured cells. He compares it to watching the engine of a passing car climb under the hood of a stranded truck and drive it away.

  17. aairfccha says:

    From the paper: “Sometimes a dark boundary line in the middle of the border regions could be seen in the bright-field images (Fig. 1D and fig. S1). This boundary line weakly stained with ER-Tracker, MitoTracker, and a plasma membrane stain”

    Does that mean that even the cell walls reform?

  18. The Arnold says:

    This is like the mercury-looking guy from Terminator…. it’s split into a thousand little balls that get together and re-create him…

  19. Zemyla says:

    This is one of the most hardcore episodes of “Will It Blend” ever.

  20. Dionysius Rex says:

    Has anyone ever tried a similar experiment with tumour tissue, and see what “evolves” out of the mixture?

  21. Hank Roberts says:

    “Beam me up Scotty. Yeah, use the blender and the hose.’

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