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What might cell membranes look like on Titan?

  1. Feb 28, 2015 #1


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    Life on earth uses water as a solvent, but scientists have long speculated about the possibility of life existing in non-aqueous environments. Titan, Saturn's largest moon, has seas of liquid methane, and scientists at Cornell wanted to test whether structures similar to cell membranes could form on Titan. They took data from the Cassini probe to identify the compounds available on Titan, and performed computer simulations of these molecule to see whether they could form membrane-like structures. They found that one compound in particular, acrylonitrile, form bilayers that are very stable and have flexibilities very similar to cell membranes found on Earth. The researchers termed these structures "azotosomes."

    Here's the abstract and citation for the study:
    Stevenson, Lunine, and Clancy. (2015) Membrane alternatives in worlds without oxygen: Creation of an azotosome. Science Advances 1: e1400067. doi:10.1126/sciadv.1400067

    Of course, membrane-like structures are only one requirement for life, so much work still needs to be done to determine how other aspects of life would work in a cryogenic solution of liquid methane. Furthermore, all of the work in this paper is computational, so the work awaits experimental confirmation that the azotosomes form and function as predicted by the authors' molecular dynamics simulations.
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  3. Feb 28, 2015 #2

    jim hardy

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    Asimov speculated on other life chemistries

  4. Mar 1, 2015 #3
    Obviously the most important feature would be the "protein's" mechanical environment. I'm guessing the four base encoding analogs of DNA are being considered? Without the machines complex cells can't do much. I have considered EM force mechanics but you still need diverse machinery to implement the various fields constructively towards an organised metabolism.
  5. Mar 1, 2015 #4
  6. Mar 1, 2015 #5
    I don't get the "reproduce in an oxygen environment" part. I assume it is referring to these cells replicating similar to bacteria?I don't see where oxygen comes from or what part it could play?

    Sorry if I went off along the "Dr. Asimov" direction in my previous post but I get the impression this is slightly narrower into simple "early sea of life" basics. Not difficult to imagine "jellyfish" swimming around slow-motion in a crystalline-coral lined sea of methane life not-as-we-know-it, though... as they dominate the oceans of ours.
    Last edited by a moderator: May 7, 2017
  7. Mar 1, 2015 #6
    Membranes and the cell surface are NOT just lipid bilayers with proteins inserted into them. The cell surface does not look at all like what textbooks tell you or what most scientists depict. For example, this is completely wrong:


    http://www.occc.edu/biologylabs/documents/cells membranes/plasma_membrane.htm

    The membrane is covered in an extremely dense layer of carbohydrates, and sugars are not just a small decoration on the surfaces of all cells like the above figure indicates. A real membrane looks something like this:



    Notice the giant halo in figure C that depicts the capsule of Cyrptococcus neoformans. That large halo consists of a huge amount of glycans that can not be seen by light microscopy unless you use special stains. Also notice how many times larger the thickness of the halo is than the cell membrane and bilayer. The other critical building block of life that gets routinely ignored is carbohydrates. Almost every aspect of life is fine tuned by carbohydrates from virtually all cell signaling, adhesion, immune system response, to development. One major issue with non-aqeous life forms is that they do not have a carbohydrate counterpart. Carbohydrates simply wouldn't dissolve in most organic solvents. Nearly ever lipid on the membrane is modified by sugars. Nearly every protein on the cell suraface is modified by sugars. Every bacteria, virus, fungal cell, plant cell, and animal cell, as far as I know, is covered in carbohydrates. I'm sure you can make bilayers with different materials in differnet solvents, but that is about all you'll get--just bilayers. Unfortunately for Asimov, he lived before biology began to realize later on of the huge significance of glycans and carbohydrates for life.
    Last edited: Mar 1, 2015
  8. Mar 1, 2015 #7
    Is that in reference to the ATP energy cycle as in organic chemistry? Essentially it's the storage/utilization of converted sugar as a cellular energy delivery system. Could there be electrochemical possibilities as in laymen's terms battery acid which flows and distributes electrons perhaps similar to an electric eel? That will be my next line of investigation!
  9. Mar 1, 2015 #8
    No. These carbohydrates are not used for energy in mammalian cells (for the most part and ignoring Glc, although Glc too is used for glycosylating proteins):


    They're used for modifying how proteins and the lipids that comprise the cell membrane behave. If DNA is the alphabet of life, and proteins are its language, then the carbohydrates above can be considered something like an accent. In certain languages, if you say the same thing with different inflection you can mean different things, and this seems to be the way life works. A huge number of proteins are modified by the sugars above, and just by changing one pattern of sugar on a protein, you can radically alter the physiology of those proteins. Take for example alpha-d-Neu5Ac. Monoclonal antibodies are a multibillion dollar industry. There are examples of where if you add or remove alpha-d-Neu5Ac on a monoclonal, you can completely change the half-life and pharmacokinetics of the antibody. alpha-d-Neu5Ac is also extremely important for finely regulating how the immune system works. Immune cells contain in a class of molecules known as SIGLECs which recognize and bind to very, very specifically linked forms of alpha-d-Neu5Ac. Binding to alpha-d-Neu5Ac highly regulates immune response and self-recognition. How about another example? EGFR is an important cell membrane protein that is targeted with cancer therapies. If you simply add one alpha-L-Fuc to it, you completely alter the way EGFR can dimerize and signal. The extracellular matrix which is comprised of huge molecules like hyaluronic acid, chondroitin sulfate, and other glycosaminoglycans uses some of the carbohydrates above (and other not listed) and is absolutely essential for regulating something like stem cell differentiation through ECM/cell membrane interactions. The only thing most scientists know about sugars is that glucose is used for energy and that's about it. Glycomics, which essentially just the study of all sugar patterns in life, is a rapidly emerging field. The point though, related to this thread, is that life developed not only with the building blocks that make up DNA and proteins, but it also required sugar. Water may be essential for life because molecules like the carbohydrates above have an awful amount of time dissolving in organic solvents. Without the carbohydrates above, life wouldn't exist. Life requires extremely maintenance and finely tuned response to stress and environment, and one big way to do this is through rapid modification of sugar patterns on the membrane of a cell. Where is the alien counterpart for carbohydrates on a bilayer membrane that could dissolve in an organic solvent?
    Last edited: Mar 1, 2015
  10. Mar 1, 2015 #9


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    Can you fully rule out that other molecules could take the role of sugars? "We did not find them yet" makes their existence less likely, but not impossible.
  11. Mar 1, 2015 #10


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    It's probably a typo in the article, and they mean replication and metabolism in an oxygen-free environment (oxygen and oxygen-containing compounds are not plentiful in the atmosphere of Titan).

    In agreement with many of the commenters, showing that bilayers can exist in liquid methane is very far from showing that life could exist in liquid methane. We still have no idea what molecules could take the place of proteins, nucleic acids, and carbohydrates in such an environment or whether they could support robust metabolic processes at such low temperatures.
  12. Mar 1, 2015 #11
    As a scientist, of course you never say "never" unless it is proven otherwise. What other molecule could possibly replace the role of sugars? This would require elements that can easily form chirality (we all have nightmares of all those hexose fischer projections from organic chemistry don't we?)---which essentially limits you to group 14 elements. Rare exceptions for atoms like phosphorous could in theory make a sterocenter, but it would be almost chemically impossible to synthesize a ringed structure from phosphorous with chirality at each center. Back to group 14 elements--even silicon has an extremely hard time forming chirality. If silicon has trouble forming chirality, you simply will not have molecules in enough quanitity that are sugar like.

    DNA is something like 2 meters long and still does not directly encode enough information for life. The 28,000 or so proteins that DNA encodes for need to modified by the extraordinary complex set of sugars and glycans to generate the hundreds of millions or even billions of distinct molecular species at any given moment in time that are found in and on a cell. The complexity of sugar coated life is encoded in the chirality centers that define sugars, the number of oxygen atoms that are in a carbohydrate ring, and the alpha/beta linkages that can form between sugars. Just from a chemical standpoint, it is quite inconceivable that a "sugar" like molecule could exist that doesn't require carbon and oxygen. Without those two elements, you practically don't have any class of molecules that could even be remotely similar to sugars. If you don't have sugars, and the DNA code can not fit enough information to directly encode all the molecular species needed to run a cell, then an alien life form that wouldn't use sugars would probably need to expand the size of its genetic code by orders of magnitude. How would or could that fit into a cell like structure? If sugar like molecules are required for life, then they'll need carbon and oxygen, and with those two elements comes the need for water.
  13. Mar 1, 2015 #12


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    Well, Titan has carbon and hydrogen in huge amounts. Nitrogen is there, too. Oxygen is more problematic, but there is some oxygen present. Now we need some organic compound that fits well into the membrane and the surrounding hydrocarbon environment.
  14. Mar 2, 2015 #13

    Andy Resnick

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    Cryptococcus is a fungi, not a mammalian cell. The cell wall/membrane of different cells (gram-positive bacteria, plants, etc.) are very different in structure.

    That said, it is definitely true that most proteins undergo post-translational modification, but I would hesitate to claim that mammalian cell membranes are "covered in an extremely dense layer of carbohydrates".
  15. Mar 2, 2015 #14

    jim mcnamara

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    Cell wall/membranes are really very different across kindoms. The archaea are thought to be most like early cells, compared to all living things here on earth. Their membranes are very unlike fungi - or procaryotes or eucaryotes. The cell membranes have unique phopsholipids Many of the species in this kingdom are extremophiles. It is possible these differences are relic adaptations to extreme temperatures, like those on Earth in very early times. Their membranes are not all like the one pictured above.

    -- Albers SV, van de Vossenberg JL, Driessen AJ, Konings WN; Van De Vossenberg; Driessen; Konings (September 2000). "Adaptations of the archaeal cell membrane to heat stress". Front. Biosci.

    Found a graphic: http://en.wikipedia.org/wiki/Archaea#mediaviewer/File:Archaea_membrane.svg
  16. Mar 2, 2015 #15

    True--cell wall is depicted and I misspoke (I pretty much only think about mammalian cells 99.9% of the time). But the main point I was trying to get across is that the outside of all known cells and even viruses are coated in sugars. cell walls in fungi and bacteria are themselves synthesized out of polymers of sugars (glucan, chitin and peptidoglycan for example). Nearly every protein embedded in the cell wall is modified by sugar.

    It depends on how you define the glycocalyx. If you include things like GAGs, the glycocalyx could be 11 um thick; compare that to the nm thickness of the cell membrane. I'd aruge that's pretty dense.


    The point though related to this thread is that another class of molecules-carbohydrates--is required for life. It's nice to think about things like silicon potentially replacing carbon, but with silicon comes the problem of things like trying to obtain chirality which is extremely difficult for an atom like silicon or almost any other element besides carbon. Chirality is essential for defining the biological role of a carbohydrate. What alien molecule would one propose that could take the place of a carbohydrate and that could store as much information? Carbohydrates won't dissolve in an organic solvent. Ammonia may be possible, but then things get screwy with acid base chemistry and a molecule like a carbohydrate might have problems forming ringed structures which would make them useless.[/QUOTE]
  17. Mar 2, 2015 #16

    Andy Resnick

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    The glycocalyx is has been hypothesized to function as a 'flow sensor' not just in endothelial cells but also some of the epithelial cells lining nephrons (the proximal tubule). Heavily glycosylated mucins also cover the apical surface of airway epithelia. The apical surface of cells I work with, epithelial cells from the collecting duct, can be stained by wheat-germ agglutinin- this stain is directed against extracellular sugars. However, the baso-lateral membrane is not stained by WGA, indicating the membrane composition is very different. Also, I'm not sure how much carbohydrate is contained in the membranes of muscle cells and neurons.

    Glycoproteins are becoming a trendy topic to study- for good reasons- but it's hard to decipher the function, since post-translational modification is, by definition, epigenetic: what regulates post-translational modification, what diseases occur when it is dysregulated, etc. etc.
  18. Mar 2, 2015 #17

    And your research sounds precisely what we're interested in and it highlights a reason why carbohydrates are important for life! Apical/basolateral glycoprotein sorting has been shown to be regulated by the addition of sialic acid:


    The reason WGA binds to the apical surface is because WGA binds to Sialic acid linked to GlcNAc--which of course you'd expect to see on the apical surface. The fact that WGA doesn't bind to the basolateral surface does not necessarily mean that it isn't covered in sugars as well, it may just mean that it has a different composition of sugars on the basolateral surface. May I suggest you try a ricin based lectin (RCA for short)? RCA binding will be inhibited by the presence of sialic acid. Often in glycan structures, Sialic acid is preceeded by galactose and n-acetyl galactosamine. If the basolateral surface is covered in proteins that are modified by sugars that *aren't* capped with sialic acid, RCA would bind to the basolateral surface and less likely to the apical surface (if you do every try this experiment let me know how it goes).

    Not to side track too much from the original topic, but this again would highlight the critical importance of a class of molecules like carbohydrates. The DNA code contains the blueprint for proteins, but what tells proteins specifically where to go? Carbohydrates do, and that information is encoded into their extraordinary complex chemistry. If carbohydrates are absolutely critical for fine tuning biology like protein sorting, what is a viable alien counterpart for a carbohydrate that can contain just as much information but is based off of elements other than carbon, oxygen, and nitrogen and can dissolve in an organic based solvent?

    (And neurons are heavily glycosylated. Sialic acid in the form of polysialic acid polymers is present. 30% of the molecular weight of many ion channels comes from carbohydrates, and so on. As far as muscle cells, they're modified by sugars as well--but I'm not sure to the extent).
  19. Mar 2, 2015 #18


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    Bacteria traffic proteins to various proteins and localize proteins to specific locations in the cell just fine without using carbohydrate tags. Just because such a system has evolved to be essential for protein sorting in eukaryotic systems, does not mean that it must be that way for all forms of life.
  20. Mar 2, 2015 #19

    Andy Resnick

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    And it may not be essential for mammalian cells, either- for example, proteins that are localized to the primary cilium are sorted according to a ciliary targeting sequence- a 5 AA sequence:


    A protein, Rab8a, recognizes this sequence, binds to the protein of interest and together they join a protein complex (Intraflagellar transport particle, IFT) which has been assembled by another group of proteins (BBSome):


    The IFT has kinesins and dyneins that move along microtubules (the ciliary axoneme), bringing the cargo into the cilium. All proteins within the cilium and it's membrane *must* be trafficked this way, since the cilium has no ribosomes.

    None of this specifically *excludes* the action of carbohydrates, but any model for the 'essential-ness' of carbohydrates in protein sorting must account for these results.
  21. Mar 3, 2015 #20
    And what regulates the microtubules that kinesins and dyneins travel on?

    Cytoskeleton and microtuble assembly has been shown to be regulated by carbohydrates as well. I know I've gone on spiels on here before about the power of O-glcnac, but this is yet another example of where the critical importance of a carbohydrate o-glcnac has been found--in regulating intracellular trafficking protein dynamics and cytoskeletal structure. Dynein itself is also modified by the carbohydrate O-glcnac.

    http://www.ncbi.nlm.nih.gov/books/NBK1954/ (see the small paragraph on "O-GlcNAc Is Found on a Wide Range of Proteins")
    http://www.sciencedirect.com/science/article/pii/S0006291X0300175X (and table 1 there)

    In fact, the observation that a carbohydrate like O-glcNAc is critically important for protein trafficking may also explain how glucose can affect mitochrondrial motility. For example, this really interesting article came out a little while ago:

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