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I was trying to understand DNA transcription from this chapter, and there seems to be no explanation on how exactly the proteins, enzymes and other molecules manage to find each other inside the cell. How do they get attracted to each other in order to start reactions or transcriptions?

Same way, when the body secretes a Follicle Stimulating Hormone, how does it reach the follicle instead of losing its way in the bloodstream and ending up in a woman's feet or getting excreted out of the body? In minute 20 of this video, the person speaks of how medicines are first "sent" to the liver, but this MIT article says that medicines go all over the body.

At least for a wound it's an understandable process. An artery of vein is severed and any blood that was supposed to flow through it now can't, so there's an accumulation of white blood cells and antibodies there which can disable any intruders (though I'm sure they wouldn't be able to see an intruder and move toward it, but rather just probabilistically bump onto the intruder), and if the intruder enters the bloodstream it would probabilistically bump into other WBC's or antibodies and get killed. Else there's always fever to kill them.

Similarly, one study says sperm use heat sensors to find the egg. Another assumes it's a chemical signal.

I went through the information about cell signalling, signal transduction and allosteric regulation, but although they speak about receptors, they don't explain how the chemicals manage to find those receptors. It's like saying that I entered a huge college campus and found the secret place where my friends were meeting and they receive me when I met them, but there's no explanation on how I knew which way to travel in that huge campus to reach my friends. Given how accurately DNA transcription happens and how viruses know to shed their shell on entering a cell and make use of the cell's transcription mechanism, I believe there has to be a specific process through which these molecules "know" how to find these receptors. Is there any research that could throw light on it?

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    $\begingroup$ Just as I have removed "know" from your title, you should remove all anthropormorphic references from the interpretation of the sources you read — if you read popular science you will unfortunately find non-scientific expressions. So replace "finds" by "reaches", "is sent" by "is released". For the rest, the answers discuss whether after release a molecule reaches its target by diffusion or specific transport etc. But you need to trim your question which is far too widely drawn, accept your ignorance and see what answers you get before deciding that it's magic. $\endgroup$ – David Jan 29 at 16:53
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The answer given by Sadegh gives a general correct broad view. But one part of the puzzle is missing, which is molecular recognition.

Molecules bind to each other via physical/chemical interaction like forming hydrogen bonds, electrostatic interactions and other mechanisms. The sum of all interaction defines the strength of the binding. If molecules have enough interactions, they stick together otherwise not. Mind that all these interactions have a range of action (a field). Like with magnets, two opposite magnetic poles attract each other at a distance, before they get in contact. Imagine a small molecule getting close to a receptor, if they are "magnetically" compatible they will be attracted toward each other.

Indeed, molecules in the bloodstream (like the Follicle Stimulating Hormone) flow all around the body. However, not all the molecules end up in all the cells. That is because cells have specific receptors on the surface that bind selectively their target. In the case of the Follicle Stimulating Hormone, some cells, like the Sertoli cells or the granulosa cells have the right receptor able to bind that specific hormone.

In the case of a drug targeting the liver, the drug gets assimilated or injected into the bloodstream, it travels all around the body but it is retained by specific molecular interactions only (mostly) in the liver. It is not that the drug knows where the liver is, it is just forced to pass through it and then it is retained by it. The drug passes also through the lungs, but it has no affinity for them so it doesn't get retained.

Inside the cells, it occurs the same. Molecules pass all around, but they do not stick to anything unless a specific protein/receptor/enzyme is found.

There is an intricate network of interactions both inside and outside the cells, molecules randomly flow throughout this network bouncing on each other until they find the binding partner and they stick to it.

Randomness is not the only factor. Brownian motion occurs, but molecules are also actively moved by different chemo/physical stimuli causing the network of interactions to be in fact extensively regulated.

For example, during the cell cycle, the cytoskeleton is actively remodeled to favor the flow of certain molecules in determinate directions (look metaphase). The cell can also alter its own permeability, actively influencing the influx/efflux of a variety of molecules.

At the body level, the circulatory system itself forces the flow in a specific direction (from the stomach to the liver for example).

The fact is, that there are mechanisms to selectively control the flow of the molecules at any level in the body, from organs to tissues, to single cells and inside subcompartments of the cells. The topic is complex but very well understood.

I suggest a big dive into this book if you really want to get a grasp on how biological systems work.

UPDATE: As suggested by @WYSIWYG, the picture would be more complete adding a very short note (the topic is way to broad to be extensively discussed here) on chemokines which are a perfect example on how cells can respond to concentration gradients. Chemokines act as a chemoattractant to guide the migration of cells. Cells can sense the concentrations of chemokines in the surrounding environment and, usually, move toward the source of the signal following the increasing concentrations of the signal molecule. In general, it cannot be overstated the importance of chemical gradients during embryogenesis, inflammation and countless other events. Gradients effectively indicate to cells the path to follow.

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  • $\begingroup$ Perhaps you can also add a note on chemokines. $\endgroup$ – WYSIWYG Jan 30 at 10:52
  • $\begingroup$ Yes, good point. I should add something about concentration and diffusion as well. I will add it as soon I have time. $\endgroup$ – alec_djinn Jan 30 at 11:04
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It's both simple and complex. The simple answer is Brownian motion. All the particles in the cell do have mobility which is related to their mass. A small particle like a soluble enzyme undergoes random walks through the cytoplasm or nucleoplasm. Thus by having a grand number of a certain molecule you can be sure that at some point it interacts with the right target. Besides that, cells have solutions for increasing the chances of interactions by creating local concentrations of the factors in metabolic or signal transduction pathways. Look at this.

Larger Particles like vesicles are transported through cytoskeleton and motor proteins. The main reason that prokaryotes have had limitations in growing their size is lacking such a system and depending on diffusion and Brownian motion to relocate molecules.

About the complex side of the story! One might ask how some random and stochastic behaviors of molecules lead to these definitive and precise actions in the cell. You can Google up "Stochastic in cell biology" or look at this book.

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  • $\begingroup$ Hmm...I'd take stochasticity as a theory, but maintain that there should be an alternate theory too. When I learnt of Prions, I felt there has to be another explanation to how decisions were taken to create scaffolding proteins, cytoskeleton etc. There seems to be an intelligence to it. Couldn't just be randomness. $\endgroup$ – Nav Jan 29 at 13:13
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    $\begingroup$ This is definitely part of it, and indeed, I think it's an underappreciated part from the perspective of a novice, but there are also molecules that are trafficked on the cytoskeleton, which is especially important in cells like neurons that can have extremely long processes relative to the rate of diffusion. $\endgroup$ – Bryan Krause Jan 29 at 15:48
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Shortly, understanding a process called molecular recognition (as stated by @alec_djinn) under crude biological environment would answer all your questions.

Before explaining answers for your questions, to understand biochemical aspects of Transcription better, I would highly recommend to read a textbook written by Lubert Stryer.

  1. Proteins including enzymes basically work by very specific non-covalent interactions.They do so because these interactions are reversible.(For example, after one transcription cycle is over, same guy can work again and again). The inside situation at transcription site is complex as many biomolecules work in a complex coordinated manner and follow the rules of thermodynamics.The proteins have a 3 dimensional structure whose active site channel can only accomodate specific substrate molecule say DNA. (Think about a lock and key).This complementarity in-turn is achieved by complementarity in Shape, number/type of non-covalent interactions it can have, free energy considerations etc.

  2. Indeed, the drug goes all over the body. However, the specific drugs contain a chemical motif which gets only recognized by specific receptors through molecular recognition.The new drug delivery systems also make use of a phenomenon called EPR effect (enhanced permeability and retention effect).The drug which is more specific towards the target and which has more retention time in the blood is more effectively acts upon the target and others eventually excreted out through renal system.

So coming back to molecular recognition, let's take the same example you have given. Think when you entered your huge college campus you specifically get attracted towards certain girls (Imagining you are a boy) but not for all. Because those girls are in a way as your mind likes. This can be compared with large class of enzymes like peptidase which break peptide bonds.Some may break between Alanine and Glycine and some may not (as you like girls).Some other may like to break between Tyrosine and Proline.That is because those enzymes have evolved in such a way that they perfectly fit in there.Continuing, now you want to find your girlfriend. This case is more specific.Its not bunch of girls. Its only one.What will you do? You will send a message/call out loud!.Similarly, biomolecules send a message through chemical signals/secretions etc.

About sperms and eggs I know they attract through chemical signals and thermal gradient.I cannot comment much about it.

Ofcourse, all these mechanisms have been proved by researches either by direct or indirect method.Modern techniques such as Fluorescence microscopy has tremendously helped us to understand the finest things of life in its native conditions.Because seeing is believing!

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  • $\begingroup$ Thanks. This is a nice answer, but it'd have helped more if there was a mention of how these molecules learnt to locate and move toward each other. Other answers say it's just randomness (and it probably is), but when I go to a restaurant when hungry, it's not because I'm attracted to it and the restaurant has doors (receptors). It's because I know that I can get food at the restaurant. How do these molecules "know"? How do the organs that secrete these molecules "know" that the molecule could eventually reach it's target? There seems to be some kind of actual research these cells do. $\endgroup$ – Nav Feb 3 at 11:26

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