[spacetimeuser5]

I read one neurosurgeon (developing a theory of quantum biology) tell that mitochondria can develop voltage potentials comparable to a lightning bolt. Then searched a bit in PubMed and found something like still up to a couple of hundreds or a hundred milliVolts.

But I was curious, what do you think about the ways by which ligands find their receptors inside or outside cells in a dense bioelectrical and biochemical environment (as described here [0]). When I asked on stackexchange, they gave me a link about gradients and concentrations, but my question was about the very beginning of ligand's effect when it needs to find and activate at least one receptor. And no receptors seem to be able to "sense" a piece of space with a ligand's concentration, as they need direct binding of a ligand, but before this how does a ligand find a way to the receptor?

This may differ whether its a small or large molecule ligand, but my ligands of interest are ions (Ca/Mg, Na, K ,Cl; Li), peptides, anticancer drugs with metallocomplexes, ion channel drugs and similar drugs.

[0] https://news.ycombinator.com/item?id=35854316

[Balgair]

I think you're asking: how does some random bit of protein/ion/drug find it's way to a receptor for it? Is that correct?

Stochasticly. It's all random, as far as we can tell.

The things that make it all work, though, are the large amounts of receptors and binding thingys, the very small spaces, and the temperature. The cell is really kinda jam packed with stuff. But, since we're at ~97F or so, things bounce around a lot. The key here is the mean free path. Depending on the thing you're looking at, the mean free path of that thing is generally sufficient to get the pieces together to party. If not, then you start getting into really complex and hyper specific transport mechanisms. Each of those is going to be it's own little research world and will have little broad applications.

With large molecule drugs, you're likely using some clever transport mechanism with cleavages and digestion steps along the way. These are really some marvels of bioengineering.

With ions, you're just doing simple diffusion modeling, and the body very tightly regulates these ion concentrations

With peptides and these 'medium' sized things, you're looking a combination of diffusion and some hacking of the cell's machinery.

Again, I want to stress something here. We're still on the cusp of really understanding biology as a species. This stuff isn't EE. We're trying to unravel ~4 billion years of random-ass evolution, it's going to take a few thousand years for us to do that. Neither you nor I will see biology as a mature science.

[spacetimeuser5]

Yea, that's correct. Though I may probably omit proteins and large moelcules, requiring transport vesicles and any specific transport mechanisms.

Stochasticity sounds like there has been performed some theoretical modelling to infer this. But does it imply that there would be some tiny % of any ligand molecules - endogenous or exogenous - which would just by chance get "an empty run" and didn't bind to their receptors (though structurally they're fine ligands with high affinity) and would be removed via waste removal systems? Is there any experimental evidence for this, like some study using radiolabelled high affinity ligand molecules to see what % of them gets into "an empty run"?

The mean free path seems sort of sensible in the extracellular space, though it still seems that the variables affecting mean free path (large amounts of receptors and binding thingys, the very small spaces, and the temperature) may be not enough. But wouldn't mean free path be near zero inside cells, where every nanometer should be occupied by some other biochemical pathway/reaction or bioelectric activity?

>>Neither you nor I will see biology as a mature science.

I personally wouldn't care a lot about proving anything to anybody in some absolute sense, but first of all to prove instrumentally and make stuff work for myself at least. I think that any biology student with the descent understanding should have some mini lab for personalized medicine (as e.g. Sinclair mentioned that his recent research on using 6 chemical compounds for OSK epigenetic reprogramming (rather than bulky viral vectors) can be done by any biology student).