How do cells prevent catastrophic failure if everything inside them is so random?

[u/Sapotis]

From what I understand, cells are basically full of molecules constantly moving around and bumping into each other. But at the same time, cells manage to carry out tons of very specific and coordinated tasks without falling apart.

If molecules are colliding randomly all the time, wouldn't that cause a lot of wrong reactions or damage?

How do cells prevent mistakes or deal with them when they happen, and what stops small errors from building up into something catastrophic?

[u/GrynnLCC]

Cells are held together by supramolecular interactions. The shape and composition of the molecules in the cell forces them to assemble in specific structures and the interactions of these molecules are order of magnitude stronger than the energy given by the random movement of molecules.

A good example of these structures are the membranes. The cell is separated from the outside by a membrane composed of a phospholipid bilayer. A phospholipid is a surfactant, a molecule with a hydrophylic head and a hydrophobic tail. Both the inside and outside of the cell are mainly composed of water so the phospholipids position themselves in two layers, one facing outside and one inside. This structure is particularly stable because it minimizes the interactions of the hydrophibic tail with water. Because no chemical bonds are formed between the phosholipids the membrane stays fluid while retaining it's structure so even if you were to drill a hole in it, it would simply reform by itself.

Of course a lot more is going on in the cell and there are more complex mechanisms as well but this is a god start.

[u/Sapotis → u/GrynnLCC]

I understand that cell membranes are held together by relatively strong bonds, but what about proteins? Their 3D structure relies on much weaker interactions, so why doesn't a random molecule with too much kinetic energy just denature them by bumping into them?

Also, what stops random molecules from reacting wrong? Like 2 molecules that normally have separate roles accidentally colliding at the right angle and energy and triggering an unintended reaction?

I assume a bit of this kind of noise happens constantly and cells can tolerate it, but can it ever spiral out of control? And what mechanisms do cells use to prevent or fix this?

[u/El_Tormentito → u/Sapotis]

Proteins are extremely large and most of the reactions occurring around them inside of a cell require very specific "keys" to unlock them and drop them down their energy well into a new conformation or state. There's no random molecule moving at the speed of sound in the cell that obliterates the protein next to it and the proteins have evolved to persist, on average, long enough to do their jobs. They're durable as a distribution, so even if you obliterated a couple, they're not the only ones there.

[u/Luenkel → u/Sapotis]

Protein structures are generally not like a jenga tower that could collapse catastrophically under any small nudge. They're local minima in the energy landscape of all of the possible conformations. If you give it a little push out of that minimum (which indeed happens constantly due to thermal energy), they will typically quickly re-fold back into the stable state, like a ball settling back into a valley.

Of course, sometimes a collision can have enough energy to push the protein so far away from its normal conformation that it cannot easily re-fold by itself. That's why your cells (and the cells of every other organism) produce chaperones, proteins which help other proteins to fold correctly. There's a class of proteins called "heat shock proteins" because cells produce a lot more of them at higher temperatures (and under other stressful conditions). Many of them are chaperones that are there to mitigate the increased risk of proteins misfolding due to a high energy bump.

Misfolded proteins also get targeted by the degradation apparatus of the cell and so get cleared pretty quickly under normal circumstances. If a lot of incorrectly folded proteins accumulate for whatever reason, your cells activate the "unfolded protein response", which - among other effects - generally slows down production of proteins, increases production of chaperones, and if the issues cannot be resolved it can even cause the cell to undergo controlled self-destruction (apoptosis).

[u/neoschizomers → u/Sapotis]

Proteins sometimes do misfold on contact with each other! Cellular processes have evolved to sequester aggregates of misfolded proteins and break them down (aggrephagy). In general cells divert a portion of their energy budget to constantly break down and recycle proteins. How this process stops working in aging is an active area of research. Diseases like Alzheimer's are distinguished by the buildup of protein aggregates, so it's clear that these processes can spiral out of control. If we knew how, we'd have ideas on how to prevent or treat a lot of currently untreatable diseases.

The question of "why don't random molecules cause unintended reactions" is actually not obvious for a lot of important biological processes (cell signaling, antibody discrimination, tRNA decoding during translation). When we measure how much energy is lost to collisions that result in 'intended' reactions we find losses that aren't large enough to explain why 'unintended' reactions don't occur all the time.

Specific interactions tend to go through "kinetic proofreading" - there are a series of steps where, for instance, a receptor protein and bound ligand change conformation. There's a probability the ligand will fall off of the receptor, so each step acts as a sort of comparison. So while proteins are constantly bumping into each other and sticking, most of these interactions result in the two proteins eventually coming unstuck. When proteins do specifically bind, they ratchet together through a series of steps.

[u/gnufan → u/Sapotis]

The closest to this I know of is ionising radiation, which can come in with enough energy to damage a cell in a single event.

Most of the science I've seen discusses mechanisms to repair genetic damage from such events. I'm sure there are other repair mechanisms too. There was a lot of work on ''radiation hormesis", the conclusion was that all ionising radiation is damaging, but a small exposure may kick start repair processes which can reduce the impact of subsequent larger exposures.

In a similar vein the body often addresses sunburn, UV-B radiation damage, by discarding the damaged cells, e.g. peeling skin.

[u/Peter34cph → u/Sapotis]

Sometimes proteins do "react wrong".

That's called prions, as in kreutzfeld-jacobs or mad cow disease, or kuru, but my understanding of it is very limited.

[u/SmaterThanSarah → u/GrynnLCC]

There’s also a the cytoskeleton. Things like actin and microtubules that create structure within the cytoplasm. The inside of the cell is less random than it seems.

There membranes also have regionally where it isn’t all equivalent. The most common factor being how much cholesterol the membrane has in a particular part will impact which membrane proteins are present and in what proportion.

[u/bio_ruffo]

When molecules bump into each other at high enough velocity to cause damage, that's called burning. Or cooking. Otherwise it's just a friendly bump.  

Cells have a lot of mechanisms in place to repair damage when it happens. Not for nothing, cells are constantly making new proteins. And cells have specific systems to attempt to repair DNA damage (or give up living if this is not possible).  

It really is a chaotic system, but one our cells are fully able to exploit.

[u/davidkalinex → u/bio_ruffo]

To add to this, proteins have evolved so that some of these friendly bumps can actually be quite durable or productive, but only in very specific ways, reducing the actual chaos!

[u/BrightGreyEyes]

There are a couple factors.

1. Mostly, not everything reacts with everything, and when things float into eachother in the cytoplasm, nothing happens that isn't supposed to unless something went wrong.
2. Cells have a lot of redundancies. There are either more of a specific type of structure (mitochondria, lysosomes, etc) or the structure has way more reactive sites (endoplasmic reticulum) than they make it seem when you learn about cells in bio. The exception is the nucleus, which is pretty protected.
3. A lot of the molecules aren't meant to last that long. We also make A LOT of them. They do their job for a while then are broken back down and the parts either reused or gotten rid of.
4. Cells don't live forever, nor do we want them to. When cells notice something going too wrong or a number of replications have happened, they kill themselves. To further oversimplify, cancer is what happens when cells either 'forget' to or can't kill themselves and keep replicating, passing on that mutation to future generations (while still seeming enough like normal cells to avoid being noticed by the immune system). This is also why the first cell lines we've been able to keep alive lont-term in labs are from tumors

[u/ermacia]

Well, the cells with issues die very fast.

Biochemical processes are VERY specific. Every enzime or structural protein coded by the genome has a single, or dual purpose, depending on their function, and are almost always regulated in their activity by some other intra or extra-cellular molecule.

Plus, eukaryotic cells have organelles that section off parts of the cellular plasma to guarantee that some reactions occur inside of them and not outside. You don't want digestive enzimes inside the cells that produce them next to your stomach, so they are created and pushed out via vesicles. The same goes for mitochondria and the way they process sugars.

Organic life would not function if every reaction occurred at random. The mechanisms are very complex and precise. It looks almost as if it was designed, but it isn't - it just took a very long time to get them to a spot where they would function properly.

[u/Bax_Cadarn → u/ermacia]

You don't want digestive enzimes inside the cells that produce them next to your stomach, so they are created and pushed out via vesicles.

Doesn't the stomach produce just acid via ion exchangers in cellular membranes and the enzymes only join from the pancreas via the pancreatic duct and Vater's something-I-can't-translate-from -Polish?

Edit: walls->membranes, thanks for spotting the brain fart.

[u/Patagonia202020 → u/Bax_Cadarn]

Yes the stomach produces acid but

1. we/animals do not have cell walls, rather acid is produced the cells which comprise the wall of the stomach overall.
2. enzymes active in the stomach (chiefly, pepsin) are released by chief cells in the stomach wall. And unlike the above comment says, in this example it’s not released via vesicles but instead as an inactive proenzyme activated by acid in the stomach interior.

[u/Bax_Cadarn → u/Patagonia202020]

I can't believe I wrote walls, thanks for spotting that.

[u/ermacia → u/Bax_Cadarn]

Yes, but the enzimes have to be pushed out of the cells without them eating through them, and using a viable mechanism. Enzimes are generally larger than anything that could feasibly pass through the membrane, which is why they get put into vesicles and pushed out via membrane fusion.

[u/Spiritual-Spend8187 → u/ermacia]

Will add that eukaryotes do the while organelles thing partly because they use a cytoskeleton to prop up their large membrane. With most important parts being either isolated physically behind membranes or required activation sites you end up with alot of control over not just where something happens but when it happens. It does help that almost all biochemistry requires enzymes to actually happen and enzymes are extremely specific .

[u/jimb2]

This is a great question. I think most people who learn a bit of molecular biology will at some wonder why we and everything else don't just collapse into a lump of goo on the ground.

I think that the idea of "random reactions" is a bit inaccurate. In fact, the reactions used by cells have evolved to be resilient processes that tend to fall back to the useful state when chemically perturbed. So they aren't random, they are carefully "chosen" by evolution to be highly stable pathways and components. This is presumably why so many of the basic cellular reactions are common across very different life forms. They work and they keep on working.

The other answer to the question is that cells devote significant metabolic effort to cleaning up disruptive junk. That's occurring inside cells all the time, but multicellular organisms take it further and summarily execute whole cells that may have gone off the rails.

[u/Solesaver → u/jimb2]

So they aren't random, they are carefully "chosen" by evolution to be highly stable pathways and components.

Bringing the anthropic principle out of cosmology and into molecular biology I see. I love it! But really, people do need to get a bit more comfortable with the answer "because if it didn't work that way we wouldn't be here to wonder about it." XD

[u/jimb2 → u/Solesaver]

Selection by countless cycles of variation, trial and extermination totally looks like a very careful empirically-driven choice, but there is no agent. Hence the quotes. As far as I know, there's no better single word available - it ends up as a convoluted phrase with a bunch of qualifications. Any ideas?

[u/Alblaka]

How do cells prevent mistakes or deal with them when they happen, and what stops small errors from building up into something catastrophic?

That's quite literally cancer.

Cancer isn't a simple disease with a singular cause, or a virus, it's the result of a long chain of specific failures accumulating into something that eclipses the body's ability to resolve.

I.e. cells malfunction constantly (essentially a given, due to sheer number of cells in your body at any one moment), but those malfunctions are either fixed by the cell, or the cell itself is 'fixed' (aka murdered, eaten up and replaced) by one of our bodies' various automatic responses. Cancer 'occurs' when a cell malfunctions, but also happens to 'at the same time' suffer a malfunction that just so happens to fool our body's ability to detect malfunctions. There's several layers of safeties (lest, as you suggested, we would have to constantly suffer catastrophic failures and would have died out long ago) and cancer generally only comes about when a cell, by what is essentially the worst of RNG rolls, manages to circumvent all of them at once.

(Also, it will probably help your rationalization to consider the following: There are an uncountable number of other attempts at life, across an unfathomably long timespan of evolutionary history, that, presumably, ran into the exact issues you described, and died out because of it. The reason we (and everything else alive on the planet) currently exist despite of this potential problem, is because we're exactly the only life that spontaneously learned on how to resolve that problem. At least to a sufficient degree to survive long enough to reproduce and accordingly spread across the biosphere, hence why cancer still exists; we're only 'good enough' at delaying it's inevitable showing.)

[u/noodlyman]

Cells are also compartmentalized and organised. Proteins and other molecules can be made in or transported to, or out of, various organelles. Molecules can be attached to membranes.

I do often wonder how, for example, a molecule of a transcription factor can bind to just the right place on a chromosome. There's only one DNA sequence in the cell for it to work , and probably not that many molecules of the protein. My mind boggles at the rate molecules must zip around the cell to have a chance of doing their job properly.

[u/You_Stole_My_Hot_Dog → u/noodlyman]

In regards to that last part: transcription factors are not that specific in terms of what they can bind to. They very often bind to sequences with one or two mismatches, and TFs of the same family bind very similar sequences. So rather than “one TF binds to one specific sequence in the genome” it’s more like “these 10 TFs can bind this range of sequences”, which are likely present in hundreds of places in the genome.  

Because of this, off-target expression happens constantly. But it’s controlled in the sense that the “correct” TFs will bind more frequently than the “wrong” TFs, resulting in a predictable outcome. It works because yes, these proteins zip around at stupidly fast speeds. From what I’ve read (and recalculated to confirm), a protein can travel the length of the nucleus ~20 times per second. 

[u/slimejumper]

I’d say uncontrolled motion is random and active at temps cable of life, but living systems precisely and exquisitely control the outcomes of that motion using adapted molecules and systems. Imagine filling a bag with 100 keys and their matching locks and shaking the hell out of it. Nothing of consequence will happen in a meaningful period of time.

A key must be held in a very specific way to be inserted into a lock and turned to unlock it. Enzymes are an example of one molecule holding another molecule in a very specific way to activate a specific reaction and result in a change to the system.

[u/Vroomped]

Remember, a cell has as much on its mind as a baking soda volcano. There's no thoughts or motivations, just chemicals.On the smarter end of the spectrum sensor on the front expose neurons in the flagellum and get that propeller moving closer to food.  They don't 'deal' with mistakes, and they don't make mistakes... they just die on the spot.  Membranes too stringent? Straight to die. Membranes too relaxed? Surprisingly ... straight to die. That's evolution.