Biology vs. Trump: do we need a wall? | Liquid–liquid phase separation

Biology vs. Trump: do we need a wall? | Liquid–liquid phase separation

March 4, 2020 2 By Joana
Reading Time: 5 minutes

In a world where walls seem to be the next big thing, science shows us this might not be the answer. It seems that our cells have a new superpower: they can control the function of specific molecules by “freezing” them, without having to confine them. This superpower is also known as liquid–liquid phase separation, and it’s one of the hot topics among geeks and scientists. But what exactly are we talking about? And why all the fuzz? Some say this new superpower allows our cells to survive in extreme conditions. Others say it might be a curse and lead to diseases such as Alzheimer’s. So what is true and what is not? Grab some popcorn, sit comfortably, and enjoy the story of how two graduate students found something so revolutionary that science textbooks had to be rewritten.

But first things first

As you know, our cells are musical factories composed of various components that need to communicate with each other to make sure our bodies work correctly. These components are known as organelles, which means “little organs”. You might recognize some of them: for example the nucleus (the house of our DNA), mitochondria (the powerhouses of the cells) and many more.

Each of these organelles has different functions, but most of them have one thing in common: they have a membrane that confines them, a wall that physically separates them from each other and their surroundings. But since diversity is a beautiful thing, our cells also have some organelles that do not have a membrane (no wall).

No one really understood how these non-membranous organelles formed or how they were able to stay together and not float apart in the cell’s swimming pool that is the cytoplasm. That was the question that Anthony Hyman and Clifford Brangwynne two cell biologists, asked their graduate students David and Lindsay: “How are these organelles formed?”, “How do they stick together?”, “How do they work and communicate with each other?”, “How?”,  “How?”, “How?”

David and Lindsey must have freaked out for a bit (I know I would!) as they were just doing a summer rotation in the lab, but they accepted the challenge and started using fancy microscopes to look at these membrane-less organelles. What they found was weird. Awesome, but weird. They saw that these ball-like structures were slowly moving inside the cells, colliding with each other, and fusing into big blobs. The reason why this is weird is that this doesn’t usually happen with solid things. Imagine a game of snooker. When you hit one ball, and this ball hits another ball, they just get dispersed into different directions, they don’t fuse into one big ball.

So why was this happening with these ball-like structures? The answer was simple but groundbreaking. These structures are not solid; they are liquid-like [dramatic music!!].

How and why do cells form these ball-like structures through liquid–liquid phase separation? It’s all a state of matter

Think about water for a second. What images come to your head? A glass of water? A waterfall? A lake? Most of us immediately think of water in its liquid state. However, water can also exist as a solid or as a gas, for example, ice or condensation. And depending on their physical states, each element has different properties: ice can cool your drink, but it can also freeze your bike’s lock (ask Amsterdamers, they know). The same is true for our cells. The physical state of molecules can affect their biological function.

Now let’s go back to our story. David and Lindsey, had just found out that the ball-like structures they had been studying must be liquid-like. Instead of snooker balls, they are more similar to drops of vinegar floating in a cup of oil, slowly moving around until they encounter and fuse into each other. This process is known as liquid–liquid phase separation and is super important for controlling several cell functions.

When cells are stressed, which happens quite often, the molecules inside our cells start condensing and come together, forming these liquid-like blobs that have defined boundaries but no real restricting membrane. The more tightly packed these molecules and structures are, the more solid and stationary they become.

This capacity of molecules to change their state and move slower or faster is why this theory is so critical. If you think about it, our cells can decide if they should have many small blobs going in different directions and doing different things, or one big blob, kind of frozen, getting ready for when “Winter is coming”. So yes, ladies, gentlemen, and most of us who are in between, liquid–liquid phase separation may be the latest brand-new hot stuff in biology. But why are these blobs so important? What do they do? Why should we care? (Yes, I can hear you!).

A small blob in a cell, a huge impact on our health

Although we still need to learn a lot about how liquid–liquid phase separation works, there are a few processes in which we have seen that these blobs might be quite handy. One example is in our brain cells. The way these cells talk to each other is almost like in the old times, by sending letters. They write the message, put it in the mail, and wait until the other cells receive it and read it. So you can imagine that when our body does not want a cell to receive a certain message, it can trigger this liquid–liquid phase separation and freeze the letter, half-way through, so that it never reaches its destination. By doing that, it can control how our brains operate, and as you can imagine, if it freezes the wrong letters, it can also affect vital functions such as memory or movement. And that’s what happens, for instance, in certain neurodegenerative diseases such as Alzheimer’s or amyotrophic lateral sclerosis (ALS).

Another example of why liquid-liquid phase separation is essential is when cells are exposed to different stressors like cold or nutrient deprivation. In those cases, it works as a survival mechanism. By creating big blobs that stay still, our cells don’t need to spend so much energy and can enter a kind of hibernating mode and wait for the storm to pass.

In sum, the lack of physical walls allows these non-membranous components to quickly and easily control the number of different molecules in the cells, which is quite cool. Right?

Well, as you know by now, after the awesome post written by our Latino-Viking Santi the First (yes, you are also entitled to an “endearing” nickname), things are never black or white, nor good or bad. The same is true for liquid–liquid phase separation. This fascinating and yet unexplored mechanism in the cells can quickly and easily become ugly if our cells don’t fine-tune this process and end up forming too many big blobs and ball-like structures or dissolving molecules at wrong places or times, bad things can happen. Some studies have linked these blobs to diseases, such as cancer, neurodegeneration, and infections. So for good or bad (or ugly!), one thing is sure, many scientists are convinced that liquid–liquid phase separation is an exciting new field in biology that deserves our attention and understanding.

So that’s all folks. It seems that just like the US, some of our cell components don’t need a wall (yep Donald, you read me!!). There is still a long road ahead to fully understand how liquid–liquid phase separation is regulated and how we can use this process to understand better how our cells work. But that’s the cool thing about science, right? We are constantly learning.

And speaking of that, keep an eye on the Embassy if you want to learn why the heck elephants don’t develop cancer (or do they?) or what is Big Pharma hiding from us.

Until then, stay awesome!

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