How do cells determine what size to grow to before dividing?

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How do cells determine what size to grow to before dividing?

In: Biology
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It’s not necessarily about how big they grow. Cell division is regulated by proteins called cyclins, and so whenever a cell is triggered by those proteins, it will begin to divide. Then, when it’s divided enough (such as, it starts running into other cells) it’s triggered to stop. If something goes wrong during that process, that’s how you get cancer (cells dividing uncontrollably and not listening to the signals that tell them to stop).

It sounds like a simple question, but it isn’t. I was actually doing my PhD on precisely that topic some years ago before changing labs. The short answer is we don’t know. It’s actually amazing that we don’t know even whether cells grow in size linearly or exponentially, and whether the relationship between size and mass is constant. There have been some fantastic technological leaps recently that allow us to measure single cell mass, lab I worked in had an instrument that could measure it to the the picogram scale while the cell is alive and adherent, for days. So I expect we’ll have an answer soon, but so far there are some hypotheses:

Hypothesis 1) geometric mechanism, more likely in rod shaped bacteria and yeast than mammalian cells. Here the cell would sense its size by relating surface area to volume. For most cell shapes, these two don’t increase hand in hand. So one mechanism is: if a cell produces a critical component or molecule that is needed to trigger cell division (given an external proliferation signal), then as soon as it reaches a given size, the molecule’s concentration at a particular peripheral subcellular location would reach a certain designated level that can trigger division.

Hypothesis 2) landmark mechanism, more likely a later mechanism in organism development, after the establishment of these landmarks. In this hypothesis, cells keep growing until they reach a certain landmark, then they know they grew big enough to divide (again, given an external proliferation signal). We already see this mechanism in other biological phenomena, like lateral inhibition, where if each cell has a receptor and a ligand on its surface, then as soon as cells have enough contact, enough of the ligands of one cell would bind the receptors on another cell leading to the culmination in a signal that tells the cell to do something (like stop growing).

Hypothesis 3) titration. In this mechanism, the cell would need to produce something that increases in amount with size while having something else that doesn’t increase at all, it’s constant. Then the cell would measure the ratio, as soon as the increasing signal reaches a given level relative to the reference yardstick, it means a certain size was reached. There are many candidates for this, it could be any ubiquitously required protein that is needed more when the cell is bigger. And for the yardstick, it could be just a protein whose production cannot be regulated so you get just the gene dose that depends on the amount of DNA, which is constant, or even the amount of DNA itself.

As you can see… We don’t have any idea really, lots of valid hypotheses, lots of evidence but nothing solid. We are pretty certain cell size is regulated, because it’s unbelievable how homogenous cell size is (of one type). And even if you start with variable cell sizes of a given type, they converge rapidly after few generations.

Here’s a good review on the matter but there are many many more (and books too if you’re interested) :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744813/#!po=0.625000

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