Social lives of cells

Our bodies are made up of trillions of single cells all working together - common idea is that they are inert, almost like bricks. Alpha Yap, professor of cell biology at the university of Queensland in Brisbane, Australia, is keen to show that this idea of static cells simply isn’t true. Kat Arney caught up with him at the Royal Institution, where he was giving a lecture, sponsored by the Company of Biologists, entitled “Touching and holding: The social lives of our cells” to find out why.

Alpha - The cell is a fundamental biological building block of our bodies. But the problem we’re thinking about as brick, is that it gives the impression it’s a very static thing and that’s not true. The cells themselves are very dynamic. They're born, they live, they die, and the tissues that are made of cells are themselves dynamic in which the cells will rearrange.

They need to organise themselves. They need to respond to stresses such as the risk of infection or toxins in the environment. They need to therefore be able to perceive as it were whether things are good and healthy, or whether they're under stress, and need to compensate in some way.

Although it’s a wonderful idea to think of cells of our body like the bricks of a house, you would have to think about it as bricks that are busy, active, and actually know where they're need to be.

Kat - So how does this work then? How does say, the cells in my skin talk to each other, know that they're skin, know what they're doing and which way up they're meant to be?

Alpha - Absolutely, so what we’re talking about is communication, biological information. The truth of the matter is, there are many ways in which cells communicate with one another.

The best understood are chemical ways in which one cell will send a signal to another cell. It might be a signal that goes long distance such as a hormone in the body like insulin or cortisone, or it might be a chemical signal that goes a short distance – perhaps 1 or 2 or 4 cell diameters. That’s really quite well understood and it’s been studied extensively over decades.

What is interesting now is that we started to realise that there's another level of communication which is a level of physical communication in which cells use mechanical force to communicate with one another. They push, they pull upon one another and that constitutes as it were a complimentary level of communication that has advantages and disadvantages to the better understood chemical modes of communication.

Kat - So you're telling me that my cells are kind of poking each other?

Alpha - They're sometimes poking each other but especially the cells say of your skin, are actually constantly pulling on one another. That generates tension at the junctions between them. It’s a little bit like a handshake.

For better or worse, we interpret or we infer a lot of information from handshakes – the physicality of those handshakes. And to an extent, our cells do as well. Although my guess is they're probably more intelligent than we are.

Kat - So, they're feeling a nice firm handshake or a limp-wristed handshake or they're missing the handshake altogether?

Alpha - Absolutely, yes. And so, one idea that is starting to develop especially in tissues that are constantly, physically interconnected is that they're constantly pulling upon one another. They can feel the constant tension from their surroundings. They can sense whether that tension changes – whether it increases or whether it decreases – and they respond to that to try and restore the balance of tension.

The point is that sometimes potential stresses in the body - like a cell that’s been infected, a cell that’s been fatally injured by cigarette smoke - that cell generates different patterns of force, and its neighbours respond to that, and respond in a way that ultimately helps to protect the tissue of which they're a part.

Kat - It’s a lovely image to think of all these cells kind of holding hands together, ganging up together, and then when someone breaks that chain, you know that something is wrong. How quickly do these physical signals, these kind of shape signals pass through our tissues?

Alpha - That’s an extremely interesting point. What's I think important is that those physical cues, those physical signals can be propagated very quickly. Theoretically, depending upon the materials involved, they can be propagated as quickly as the speed of sound.

Kat - Doinggggg!

Alpha - Exactly! You could think about it like a neighbourhood watch system. It’s very sensitive. If I were a cell, I could detect something going wrong really quickly. What you sacrifice for speed is specificity. I may know something has gone wrong, but I may not know exactly what the nature of that is, which is why you have other communication cues – chemical cues that we know that provide a different form of information, albeit somewhat more slowly.

Kat - So if this physical connection is broken, you might not know if it’s something really bad like the cell has gone wrong or if it’s just a little shuffle.

Alpha - You could think about it like this – if my neighbour is ill, I sense because of the loss or change in physical connection, I sense that they're ill. I don’t know whether they're ill because they’ve been poisoned, whether they're ill because they’ve actually started to become cancerously transformed. Eventually, I need to know that. But as a first warning, all I need to know is that something is not right.

Kat - How do you measure these forces? Because as a geneticist, I know that we can measure genes being turned on and off, we look for the messages coming from our genes. If you're interested in the molecules being produced by cells you can measure levels of molecules in the blood or in cells themselves. How do you start measuring these tiny, tiny forces that our cells are generating and poking each other with?

Alpha - That’s actually a non-trivial problem because in fact, it’s very hard to measure forces. What you choose to measure depends a little bit upon what you're interested in. If for example, I was interested in a molecule that I think is responding to force, then we now have tools in which we engineer the molecules so that when they become stretched, they change the amount of light that might be emitted from a sensor.

If on the other hand, I'm interested in something much larger like a cell - the extent to which it’s being pulled or pushed - then we have tools to infer the forces. So for example, if I'm interested in the amount of tension between two cells, I can cut the junction between two cells with the laser and I can measure the recoil of that cut zone. A little bit like, if you can imagine a rubber band – the amount of tension that is present in the band can be inferred by cutting it and measuring how quickly that band snaps back.

Those are not very good measures of force directly. And so, we’re at a stage where I think we’re still developing new tools. But the other that’s important is that this is really a multidisciplinary problem. Biologists are terribly bad – at least biologists like me are terribly bad - with physics. Some of us are innumerate and really, what we need to do is to collaborate with physicists, mathematicians, engineers. Because each of the different disciplines brings a different expertise to address the problem.

Kat - And for biologists themselves, is it going to be more and more important that we think of cells as physical objects of the forces, the squishing, the connections, the communications, rather than just being sort of blobs that are turning genes on and off?

Alpha - I think that’s absolutely the case. I think that in a way, what we’re talking about here is a very old science - the impact of forces on biological systems and bodies really appeared in the late 19th century. One of the classic texts is D’Arcy Wentworth Thompson’s great book On Growth and Form, how geometry and physical factors influence body form and shape.

But all of that went out of favour with the genetic revolution and the sheer power of molecular genetics. That’s not to say that that isn’t extraordinarily powerful. But as you say, at one level, we are physical objects – we hurt when we fall, we move through space, and that physicality is something that also coordinates biological behaviour.

Kat - Alpha Yap, from the University of Queensland in Australia, speaking to me at the Royal Institution. Thanks again to the Company of Biologists for sponsoring his talk.