Bacteria Bionumbers

There’s a thought experiment I’ve been meaning to do - perhaps posting it publicly will help muster the focus to actually finish it off.

Roughly - what are the physical constraints on communication bandwith between bacteria, in some fixed amount of time?

Ultimately, I’d like to know:

  • How many bits are typically transferred to/from one bacterium via quorum sensing, over a typical generation?

    • Ideally, some sense of how many different kind of things the bacteria is hearing or saying, from this.

  • How many bits are typically transferred to/from one bacterium via conjugation, over a typical generation?

    • Ideally, some sense of what types of things are transferred.

    • Can only transfer literal conjugative plasmids (is this true?) - lame!

    • I would guess each bacteria gets 1 / generation, there are maybe 6-8 genes transferred? Would love to check though.

    • F pili that allow the transfer of single-stranded DNA have an outside diameter of ~8nm, which is smaller than that of the larger nanotubes observed in B. Subtilis?

      • https://www.cell.com/fulltext/S0092-8674(11)00016-X?large_figure=true

    • 1-10 conjugative pili / cell

      • https://bionumbers.hms.harvard.edu/search.aspx?trm=bacterial+conjugation

    • https://journals.asm.org/doi/full/10.1128/aem.65.8.3710-3713.1999

      • If I understand this paper correctly (and I’m not sure I do), in a certain experimental condition there were ~1 per 1000 cells that could have plasmids had plasmids transferred after 2 hrs?

    • https://www.nature.com/articles/s41467-023-35978-3

      • Oh, this looks pretty cool

    • www.science.org/doi/abs/10.1126/science.1153498

      • This paper claims F-pilus mediated conjugation at distances up to 12 um

        • Apparently this is an area of active debate https://www.pnas.org/doi/abs/10.1073/pnas.2310842120

          • Apparently the pilus can retract to bring cells into contact before transfer?

          • This paper claims that ~6% of conjugation events are mediated by long-distance transfer.

      • It looks like conjugation began after ~5 minutes, and over the course of 30-40 minutes.

  • How many bits are typically transferred to/from one bacterium via transduction, over a typical generation?

    • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068684/

      • This paper cites ~1 in ~10^7 E. Coli transduced / hour, where conjugation is cited as 10^3x faster

  • How many bits are typically transferred to/from one bacterium via nanotubes, over a typical generation?

    • My guess: How big are they anyway, and how many typically from one bacterium?

    • Canonical paper where they are described here: https://www.cell.com/fulltext/S0092-8674(11)00016-X?large_figure=true

      • Wow, it’s like…they were very connected by nanotubes in this paper (as in, most bacteria in these cultures seem to have been connected to at least a few others)

      • From photos, looks like 2-4 connections/cell

      • I would guess they are ~10^-7 m across so 10^-13 m^2 cross sectional area

        • They say tube length ranged up to 1um, width ranged from 30-130nm

      • Woah, they also have small nanotubes that ‘stitch’ cells together?

      • Can exchange nonconjugative plasmids

      • I’m curious how many species this applies to, and what % of species that do have this property aren’t connected

    • What’s the difference between a nanotube and an F-pilus?

  • How many bits are typically transferred to/from one bacterium via membrane vesicles over a typical generation?

  • How many bits are typically transferred to/from one bacterium via gene-like transfer agents, over a typical generation?

    • https://www.science.org/doi/10.1126/science.1192243

      • This paper claims that gene transfer frequencies are 10^3-10^8 times the frequency for transformation, and 10^6-10^7 that of transduction - I have no idea how to evaluate these claims

  • How many bits are typically transferred to/from one bacterium via transformation, over a typical generation?

    • https://www.annualreviews.org/doi/full/10.1146/annurev-genet-112618-043641

      • This paper puts rates of transformation at 80-100 bp/s - presumably this is the rate once it has already started

    • https://www.cell.com/cell/pdf/S0092-8674(19)31277-2.pdf

      • It seems like ~80%+ here of cells did something in response to DNA in the environment, I’m curious though what concentrations of DNA are naturally present

    • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC372978/pdf/microrev00022-0281.pdf

      • This paper mentions DNA adsorption as rate-limiting for transformation

  • How many of these mechanisms does a ‘typical’ bacterial strain have (realizing how ridiculous that might sound)

  • How do bacteria communicate through electricity?

    • Which bacteria electrically signal? How do we know it is only them? How did we find out about this initially?

  • On what lengthscales and timescales does communication in bacteria happen?

    • What are the physical limits on communication - as in, communication on lengthscales?

    • https://www.cell.com/cell-systems/pdf/S2405-4712(18)30245-X.pdf

      • This paper cites bacteria coordinating metabolic activity over hundreds of cell lengths

    • Do cells typically signal in 2 dimensions or 3?

    • What are all the different lengthscales associated with communication between cells?

Here are some questions I’d like to find bionumbers for, for a start:

  • How many receptors are there / bacteria, how many likely to be involved in communication?

    • I think this number should be ~10^5 (around 10% of protein expression), but need to verify

    • This link would suggest oom 10^4-10^5 / bacteria for a single type of chemotaxis receptor, so this estimate feels about right - it can’t be more than the oom of proteins in a bacteria (10^6), and ~10% feels right to me when I think about it (well, I’m curious if I did a literal packing estimate and thought about surface area if that would still sound right)

  • Do they roughly maintain the same density over different surface areas? What governs this if so?

    • I would guess so - unless they cluster together on the cell surface? I was wrong - it seems like they do cluster together, in particular in the context of chemotaxis.

  • How many different chemicals and how much genetic information is in the extracellular environment of a bacterial culture at a given point in time?

    • Quorum sensing molecules would be in the nM-uM range? This would be ~1 - 1000 / bacterial cell volume

  • How many bacteria can talk to each other at the same time (how far can chemicals diffuse before the concentrations aren’t detectable by the other bacteria)?

    • What’s detectable? I would guess for example 1 nM (1 molecule / E. Coli volume would be too low). How does conc fall off over time? Well you secrete some burst and as r gets larger, diameter increases by 2 * pi * r, so conc falls off as 1/r, which assumes they all shoot outward which they don’t but whatever. How much gets secreted initially? Well, I could just hazard a guess that it’s oom stuff leaving the cell, maybe * 10^-1 or 10^-2? So, that’s ~10^13 / 20 min so 10^11 / 20 min - so 10^8 / second. Still seems like a lot - I wonder what that is compared to other metabolites in the cell. Anyway, let’s uh say that’s the conc over an E. Coli volume (so 10^8 nM) - um, okay, how do I get to limit of detection? Like, I can just assume the conc outside is about the conc inside for the signaling molecule.

  • What are the detection limits on chemicals by a given bacteria? What counts as an extracellular signal and what doesn’t (for example, do ion concentrations change bacterial behavior, if so how would we differentiate between those and quorum sensing? What ‘simple’ chemicals do bacteria routinely change in their environment?)

    • What chemicals do bacteria detect?

      • Things that are bound by extracellular receptors

        • https://quorumpeps.ugent.be/

      • Things that diffuse into the cell and cause some change in behavior

      • How many channels are in an E. Coli membrane?

      • How many active transporters are there in an E. Coli membrane?

  • What is the time delay between one bacteria deciding to say something and another bacteria hearing it?

    • Diffusion time between two bacteria

      • Is there ever active transport of signaling molecules extracellularly?

      • What is the average distance between two bacteria in a saturated culture - I would guess oom 10^-6-10^-7 m?

      • How long does it take a small molecule to go 10^-6 m on a random walk?

    • Does this diffusion time match what we see from experiment?

  • Do bacteria always have to talk to all the other bacteria? They can never talk to just a specific other bacteria? What other examples are there of public communication like this, how does this link back to passive diffusion as a surprisingly central mechanism in biology that doesn’t jive with (for example) computers?

    • I guess this is mediated by receptor expression

    • So, bacteria are unique to the extent that they present a surface to the extracellular environment that is unique

  • What are all the messages of intermediate sizes between a single molecule and a whole bacteria? Do bacteria ever merge?

    • I’ll bet some bacteria merge

    • What is the most frequent (physical and sequence length) size of message exchanged? What are the distributions for both of these properties?

  • How many different bacterial species are there, and how are these properties distributed across those species?

    • What does it mean to be a different species? To have a different genome? That you can’t merge with the other bacteria any more?

    • How openly accepting is the transformation machinery bacteria use - could you, hypothetically, turn any bacteria into another using naturally occurring transformation machinery?

  • Are bacteria all just talking to one thing (the state of the environment) instead of each other)?

  • How much do concentrations of things like quorum molecules vary across space in a typical tube of bacteria? How heterogeneous is genetic information across space?

    • Do bacteria ever structure these molecules extracellularly (like, clumps of DNA or molecules captured in some structure)

  • Do bacteria ever secrete things which use active transport to move? Why/why not if so?

    • I mean, how would it know where to go? Maybe it would have to follow a small molecule gradient and there you have it, a tiny bacteria.

  • How much mass does a typical bacteria secrete in one generation?

    • Let me guess - okay, 20 min to do it, what’s a good parameter for metabolic rate? How fast do enzymes typically do stuff - is ns way too short? Well, you can cross an E. Coli in 10 ms if you’re a protein and small molecules would be maybe a second or less, then? Slippery little creatures.

    • Let’s say ~10^13 water molecules in an E. Coli (is that totally off - I mean 10^10 carbon atoms so sue me). Well, a bunch of those are going in and out - well, do I care about net or some other form of mass transport. I mean, I don’t think I care about water molecules, sorry water molecules. What do I care about? I guess interesting stuff - stuff that could change the inside or outside by being secreted, that feels a bit more intentional. Hmmmmmmm - if 25-50% of E. Coli surface area is proteins, let’s say 2.5-5% of its area is channels, let’s say molecules go through at (fuck me, I don’t know) - literally no idea okay let’s go consult the mol bio bible. Well, okay, do many enzymes do 10-100 things per second? Lol that is not a good proxy for ion channels - but my best other is 10ms for a protein to cross a cell, so honestly ~10^2/second is kind of not crazy. Let’s go with that - then 10% ion channels, I know oom 10^6 proteins in the cell so I would guess around 10^5 are surface so maybe 10^4 are ion channels. Does that work - if each is like 10 atoms across, 10^2 * 10^-20 m^2 for one, 10^-14 m^2 total, surface area of E. Coli something like 10 (4 pi smooshed) * 10^-12 = 10^-11 - haha after some gesticulating that is within 1 order of magnitude of 1%, so maybe I undercounted ion channels or am totally wrong about everything. But that’s cool! So let’s say 10^4-10^5 ion channels, maybe 10^2-10^3 things go through / second (such nice sequential exponents), so 10^6-10^8 things leaving (or entering? I’m not going to thing about that now) the cell each second, if each is ~100 atoms that is 10^8-10^10 atoms which is HOLY SHIT that is as many carbon atoms as are in a bacteria going through each second? And that means that in 20 min (I hate minutes so goddamn much, that is 10^3 seconds thank you very much) that is 10^11 - 10^13 atoms upper bound. So, upper bound, as many atoms as are basically in the cell go in and out each generation.

      • What gives? (Orphan exclamation from an earlier annoyance)

    • WAAAAAAAAAAAAH that is so freakin cool - like, a bacteria says goodbye to as many atoms in one lifetime as it is made of! Poetic, no?

      • Does the bacteria ever get sad, saying goodbye to so many atoms? Awwww.

    • Gut check on human turnover times - I mean most stuff (from ref) except CNS (again, what the hell gives there, I will be eternally curious how we figure that one out - and whether we could have built it to be otherwise) turns over on days/weeks/months. So, bacteria replace themselves faster than humans?

  • What on earth is the correct timescale with which to think about bacteria?

  • Do bacteria exhibit any cyclical behavior?

  • All of these questions, but for all cells not just bacteria

  • How thoroughly have we characterized communication between cells in multicellular organisms?

  • Does the behavior of bacteria vary when you look at, for example, 1M cells vs 1000 cells at the same density? So, does putting more bacteria next to each other result in more interesting behavior at the same density?

  • How is communication in 2D populations different from communication in 3D populations?

  • How close are bacteria typically to each other? How close in genome space (haha)?

  • How much information is exchanged between computers on the internet on a regular basis? What is a good timescale on which to think about this? Has anyone ever drawn an interesting conclusion about the world by thinking about this (maybe too functional but it seems so interesting but I’m curious how you’d summarize and make sense of that data)?

  • What are the fundamental units one should consider in a population? How does one think about fundamental units in the context of information (yay units!!)?

  • If I really really wanted to transfer as much information as possible between two bacteria, what would I do?

    • Well, I wonder how much more high-bandwith EM forces (or gravity! gosh that would be super fun to think about, although it’s not strong enough?) would be.

    • Can I just roughly estimate - if there are, let’s say 10-20 molecules that are saying stuff shuttling between cells (so oom 10^1-10^2) and the range for each is…well, either binary or some continuous thing. I’ll model it as binary for simplicity’s sake and come back for the information theory when I’m feeling in a playful mood. I guess you can say 2^10-2^100 things - lol really matters which one I guess.

    • Then, you can update based on diffusion time of a molecule between bacteria (is this correct)?

  • What are bacteria saying to each other - and on what timescales? Do they care a lot about talking in one generation? Across multiple generations? Do seconds ever matter - could they, with diffusion times?

    • Oh - proteins get across E. Coli in ~10 ms, but across a HeLa cell in 10 s - so, I’m guessing diffusion is a huge factor

  • If I had a bacterial pet, what would I want it to look like

    • Well, it would be cool if it had a lot of motors. Flagella side quest?

  • How many messages does an E. Coli get / second?

    • How does this compare to the number of messages it puts out per second?

    • How many of the messages come all the way into the cell, vs just bouncing off of the outside?

    • Could look at number of quorum sensing collisions in V. Fischeri?

    • I would guess ~1M proteins in E. Coli, 1% relevant guess (10% receptor, 10% of that) so 10^4 receptors

      • How often do receptors collide w/ signaling molecules? Wow, I have no idea

      • I would guess…well, it takes one protein 10 ms to cross an E. Coli, so less than that (proteins are bigger than small molecules and might diffuse slower, that’s a really high bar - crossing an E. Coli in straight line - and it must have bumped into a lot of things locally along the way, I’m assuming there are enough messenger molecules near the receptor to make collision likely)

        • How many messenger molecules are near the receptor? What is the average conc of a messenger molecule - more than 1 nMolar, presumably. I should check this - I would guess it’s fine, but should check.

      • I would guess more than 1 collision / ms - might be up to 10-10^2 collisions/ms, so, 1 collision every 10^-4 - 10^-5 seconds

    • God damn, what is a good timescale for E. Coli? Omgggggg

    • Well, with this, I’d predict it gets 10^4 * 10^4-10^5 -> 10^8-10^9 meessages/second (is that a lot?) -> well, I think that is (are there really 10^13 water molecules in an E. Coli, given there are 10^10 carbon atoms?). ~10^4 less than all of the molecules in the cell, I would have guessed 10^3 but that sounds about right.

  • How big is a typical conjugative plasmid?

    • From one paper, figures from ~60-200kb come up - curious what the range is for one species, and across species. About how many genes are typically transferred by conjugation? By each method of HGT?

      • I would guess 3-10 genes by conjugation (but no idea), fewer (?) by transformation and transduction (but no idea), no idea how many via nanotubes, membrane vesicles and phage-like particles

  • How much energy and matter to cells expend on HGT?

    • What is the difference between a nanotube and a conjugation pili?

  • How much of the E. Coli genome contributes to proteins for HGT or communication between bacteria?

  • How do bacteria decide to send genes to other bacteria? How do they pick the genes?

  • In conjugation, is genomic DNA ever transferred, or is it just plasmids?

  • With what methods can we directly visualize horizontal gene transfer?

    • https://www.science.org/doi/10.1126/science.1153498

      • Implicated F-pilus mediated conjugation at cell-to-cell distances of up to 12 um - but I’m not sure how

    • https://www.sciencedirect.com/science/article/abs/pii/S0147619X18300271

      • Here is a review of methods from 2018

  • How big are the stretches of DNA transferred via conjugation?

  • What do plasmids typically say?

  • What are all the ways that we have characterized lateral gene transfer? How do we look at two genomes (or many reference genomes) and make such a call?

  • Can any cells sense an electric field? How does membrane depolarization relate to this? Are all electrochemical actions of cells mediatd by ion flux across membranes - are any just, like, electric fields which somehow cause long-range communication?

  • Do cells typically signal in 2 dimensions or 3?

  • Are bacteria always talking (for example, are they always excreting molecules related to quorum sensing)? Or do they do this in bursts? Or only in certain phases? When would or wouldn’t they? Do they always want to talk but can’t (it would be good for fitness but takes up too much resources)? Is there ever a dark forest scenario where they don’t want to talk if they can help it, where they’ve evolved to hide their tracks? How often do they get messages back? How often does the aggregate message change in response to what they’re saying? Do they want to change it, are they trying to? How many components are there - really only, like, one or many? Are bacteria happy? What would that mean? Do bacteria like certain things vs others? If a bacteria wanted to have a good time, what would it do? Can bacteria play? Do bacteria ever bump into each other? How often, if so? Do they even care if another little bacteria is lying right next to them? Could they tell from receptors that sense pressure on the surface (do they have those?) or from changes in local concentration gradient (would it go down a bit if there was a - relatively - big thing right next to it that was also sucking stuff in and spitting stuff out?)

  • This is kind of silly, but could a bacteria move forward just by inhaling (kind of like could a human move forward just by swallowing and expelling water - seems possible but super inefficient, maybe it would have been possible for a bacteria if not for the low Reynold’s number)? But wait - do scallops do this? They kind of propel back and forth so it seems a bit different - like, you can open up and then close in such a way that you push a volume of water out and then Newton’s 3rd law kicks in?

  • Do bacteria talk to each other with electricity? Why would or wouldn’t they? Can they sense fields, or just specifically ion concentrations? I guess they can certainly sense gradients across their membranes. Do they like doing that? How much - is this a big part of fitness for them?

  • Do bacteria use any other weird forces? I’m still curious about gravity. If you deleted the strong and weak nuclear forces, apart from the, uh, obvious problems with individual atoms, would bacteria notice at all? Are quantum effects relevant to bacteria (is this analogous to the ‘Planck energy + average over a bunch of atoms give rise to two interesting timescales in biology)? Same for gravity - if you deleted it, would bacteria care? Particularly bacteria in the ocean? It would be really funny if you didn’t - maybe they would be happier on other planets (or small things generally) than we would because their bodies are more adapted to environments with various gravities?

  • How do bacteria interact with pressure in water? Like what does that value, specifically, mean to them? What am I using bacteria as a stand-in for? Like, a few micron sized containers that scoot around in a low Reynold’s number environment and talk to each other and are mini computers - about as big as the DNA they’re storing - inside? It’s cute how they are little bags of DNA. Could you delete any part of this and still have some interesting stuff? What would bacteria in a super high Reynold’s number environment look like? Would they be happier or more sad - would they still talk to each other as much, would they directed move more (or would random movement from the surrounding fluid still make that pretty hard). Do bacteria want things? They seem to have…some constraints, some quite physical constraints? What are the scaling laws of bacteria?

  • Why can’t bacterial populations be more than a certain size amount without losing their coherence? Can you derive this size limit? Does it exist? What are the various relevant size limits for computation? Do bacteria have cities? Galaxies? Can the cities interact with each other? Can biofilms interact with and talk to each other? Are there communities of bacteria in liquid culture - how important is it for bacteria to have neighbors that stay there.

  • Do bacteria like traveling around? Do they like exploring? Do they change their own DNA? Do they have ways to update if they did? Is there one sneaky organism at the bottom of the ocean that’s never died, it just kept updating its information so it was continuously adapting but there was only one so we never found it? Seems unlikely because….s*** happens, but it’s possible? So we don’t really know? And by definition we wouldn’t have seen it?

  • What are anti-meme biological organisms? Organisms (like the above) that, by their properties, wouldn’t be seen? Or are made to be forgotten? Like, really fun forms of camaflouge.

  • Do bacteria care about a sense of identity?

  • Can bacteria dance? Would they want to?

Thought experiments

  • How much information do bacteria exchange through HGT in a given generation? Through conjugation? Transformation? Transduction?

  • Points of view:

    I am a message, what do I see?

    In a cube of liquid, what messages are there?

    I am a part of a bacteria cell membrane, what do I see?

    I am a full bacteria, what am I hearing?

    I am a bacteria, what do I want to say?

    What fraction of the population has which genes?

    What is the communication state that a lot of bacteria have access to?

Questions

  • What does information mean (in the context of DNA transfer between cells)?

  • But what are bacteria saying when they talk to each other with HGT????? I’m dying I have to know. Is HGT ever used to transfer information about the environment - well, obviously, plasmids that encode for antibiotic resistance genes are gonna spread. But does it ever say more than that - and what would that mean? To say more than just giving a friendly bacteria a gene (haha just kidding, who knows if they are friendly) - to encode a more complex message via HGT, what would that even mean?

  • Are bacteria better at detecting things inside than outside? What does that mean? What kinds of machinery would I make to make that so?

  • How much of bacteria putting up with bacteriophages comes from the latter helping bacteria communicate through HGT? Is this true at all?

  • Can bacteria adapt within one cell, within one generation?

  • Do the bacteria know that there are other bacteria out there?

  • What is the action space of any one bacteria?

  • What is the coolest thing a biofilm has done, or can do?

  • Do bacteria ever know where the information they got came from?

    • Do bacteria ever know who they are talking to?

  • How do specific ways of communicating change the nature of the information communicated?

  • How much information does a bacteria get per second per generation?

  • What is the communication state that a lot of bacteria have access to?

  • Does local communication (for example, conjugation or nanotubes - things that involve getting a message from a specific other bacteria) in bacteria ever matter? How is it significantly different than bacteria accessing the shared communication state (ie molecules diffusing in the medium)?

  • Why don’t genes do more interesting stuff in bacteria, if they are in all of the bacteria? Why don’t they coordinate more interesting group-wide behavior?

    • Do the constraints of communication (don’t want to just through quorum sensing molecules out into the soup of the ocean) make this more feasible in multicellular organisms or a sessile community?

    • Does this mean evolution from a biofilm or multicellular community is more likely if one is later a multicellular organism?

  • What mechanisms do cells have for sticking together, or controlling the flow of information or for making it specific or local? When do they want to do this, and when do they not?

  • What did biofilms evolve into?

  • How does HGT compare to quorum sensing, in terms of what it is telling the other bacterium or the volume of information transmitted?

  • Did bacteria clump as soon as they could?

  • What concentrations of DNA are naturally present in the environment of a bacteria?

  • What’s the difference between sensing a concentration, and receiving a DNA message - how does information theory think about both?

  • How fast do bacteria get better because of HGT?

    • Antibiotic resistance might be a good example - well studied, bacteria do care a lot about it spreading. Does it spread due to differential bacterial replication or HGT though?

    • Days - weeks? What does this mean though?

    • How broadly can resistance genes spread? Can you really spread HGT through wastewater - how far away can one bacteria talk to each other? How does this work in the ocean? In the ocean, are there a bunch of genes floating around? How many? What kind?

    • How could you tell if HGT or differential bacterial replication is the primary driver of a particular gene spreading? Is one preferred? Why? Is HGT better at getting farther away? Yeah - why would a bacteria prefer to give another bacteria a gene vs replicate? Maybe it’s better for that gene to be present in more diverse environments?

  • If I could see everything in the air, what would it be?

    • How much eDNA / nucleic acid is there in the air? What does it say?

  • What about quantifying information transfer between cells in a multicellular organism?

    • What role does eDNA play here? What do extracellular nucleic acids do in a multicellular organism? Stuff shared in a membrane? Signals? How does quorum sensing in bacteria relate to signaling between cells in a multicellular organism? Did one evolve directly from the other?

    • How did signaling between cells in a multicellular organism evolve?

    • How did multicellularity evolve?

Not quite findings but questions!

https://complexityzoo.net/Complexity_Zoo < I love this so much! I love this so much!

^ I love this so much!!!!!!!

What would be similar?

  • communication modalities?

    • using different physical forces?

  • communication regimes?

  • how do you classify these? across types of thing communicated - molecules or forces. Across context - more individual bacteria, vs biofilms or multicellular organisms. and then what kind of communication - like what is it saying? how complex? what does complexity mean in this context? what does it make the other thing do?

  • maybe this is the question I’m interested in (right now, l) - how does one classify communication? what are the ‘correct’ boundaries?

  • one thing I haven’t thought too much about is what the different types of communication are in the correct way - like what does it want to be

  • what are bacteria typically saying to each other? helping each other survive? (like, helping another individual?) or ‘coordinating’? what does ‘coordinating’ involve? do cells signaling in multicellular organisms do both too? what different types of coordination are there? the cells all doing something together that is bigger than any one cell? what does that mean?

  • this is so exciting!

Findings

  • Bacterial density matters, not only for signaling molecule density but also for diffusion time (how fast they can update each other).

  • So unless they are all hanging out right next to each other, they can’t talk fast enough?

    • I mean, what, really is fast enough - 20 min for a bacteria to divide, do we really care if it’s taking 10 s for a small moleule to diffuse between them?

    • Can’t do an axon length though lol that’s like 20 days, 1 cm timescales are so last year

  • Bacteria all have access to the same shared state - with some spatial gradient, but not very specific

  • Time to share information + amount of information to share might be major factors affecting how bacteria choose to communicate (through long-distance diffusion-based signaling or through direct contact ie conjugation)

    • How true is this? For example, how different are transformation and conjugation in this respect?

  • Did we start out as a type of biofilm (would have made the the evolution of intercellular communication more easy, potentially)

    • What is the evidence for/against our evolution from a multicellular community, vs from a single cell?

  • Is the reason one would do replication vs HGT (if both are just methods for information transfer) the physical constraints on installing a large portion of one’s genome in another cell?

  • If we started off as a soup of information-containing molecules interacting, why did they evolve boundaries?

  • Could it be that there are physical limits on communication at larger lengthscales, which constrains on what lengthscales you would expect to see organism boundaries? How do structures on larger lengthscales affect or change these length or timescales (for example, vasculature or vesicle transport in neurons)

Some kind of fun facts about bacteria from this

  • They have to keep motoring along to ever really get anywhere or go see their friends (if they stop motoring at 30 microns per second, they slow down to a stop in 0.1 angstroms - what!!!), so it’s hard to see people

  • They can’t really go see a friend (man, directed individual relations are really not a thing on this scale are they, sorry guys!!!), because they do a 3D random walk (shoot along in one direction for a few seconds than twiddle around) - so they can’t really go say hi to someone

    • I wonder what that means if you’re next to a bacteria and thought you were talking to it

  • They do sometimes attach suckers to other bacteria to exchange material directly with one particular bacteria which (do they have any preference when they do this? any reason to do it with one bacteria vs another?) - does it have anything to do with the length or complexity of a message exchanged?

  • Apart from sex (the conjugation described above) all they can really ever do to talk to other bacteria is ‘shout’ (like, scream out molecules into the void surrounding them that go bumping into other bacteria) - and there’s no way to ever really say who’s doing the shouting (unless you leave entrails - DNA - lying around, which might be a bit specific but boy is that ever weird, but also kind of cool) - so bacteria are kind of hearing an aggregate shouting all the time, a hum of background noise about kind of what’s going on with the overall thing, and sometimes they have very specific interactions with other bacteria, but that’s pretty rare

    • Do we care more about specific interactions and less about the overall hum now? How would one even quantify that?

  • Bacteria are kind of always talking (or are they? how often do they generate i.e. AHL-related or quorum sensing molecules?)

Synthesis

  • Well, it basically feels like nothing is synthesized in my head

  • What would it take to chunk/load it better?

    • I still don’t know what bacteria are doing when they talk to each other!

    • What’s the right way to represent that? Volume of information flow (who the heck knows) - maybe something about the action space of the bacteria after they receive the message. I mean what can they do? They can change their ‘cell state’ (and what the heck really is up with that, is that the next latent space of biology), they can move around, they can say stuff in response.

Quorum sensing

HGT

Other

What frameworks are useful to consider when thinking about information transfer between cells?

  • Does Shannon entropy ever actually help here? Like, is it a reasonable proxy for volume of information transfer?

Sidequest

  • But how would I show that enzymes should, by definition, be able to increase reaction rates by ~10 orders of magnitude (!!!) or more? By just holding two things together? Or does that figure refer to them doing other things also?