Getting bigger without the BANG!

Life survives by being adaptable. When you blow up a balloon, it’ll stretch to a certain point, then give out with a bang. Thankfully, our tissues have a rather less devastating way to respond as we grow up and/or out.

In a previous post, I asked how my skin would keep up with my increasing waistline if I put myself on DrRiviera’s “window to weight-gain” diet. The details are something scientists and engineers are still working on, but the general answer is that skin grows when it’s stretched beyond a certain comfortable limit. Just as we feel pain if our arms are pulled too hard in opposite directions, the cells in skin also release a kind of alarm signal when over-loaded, but this signal shouts “grow!” And it keeps growing until it feels suitably relaxed again.

So what does “grow” mean in this case?

To answer this, let’s have a quick look at what tissues are and what they’re made of. Tissues are the materials that organs are made from, and include stuff like skin, bone, muscle and even blood. The main things that make up a tissue are cells and what we call extracellular matrix.

You can think of a cell as the basic living unit of a body. That is, they can survive and reproduce on their own if you give them the right conditions (note: this won’t produce a whole human body J). Different cells act as builders, repairers, sensors, controllers and communications teams: in short, they do the work. In some cases, they’re also part of the structure: your skin keeps out the rest of the world, and your blood vessels keep your blood inside, by cells holding tightly onto one another.

The extracellular matrix (ECM) is the stuff in between the cells. If cells were spiders, the ECM would be the web. When a palaeontologist digs up an ancient bone, the cells that built, maintained and lived in that bone have long gone, but the matrix remains. It’s a mix of proteins, fats and sugars (and tiny plates of mineral, in the case of bones and teeth) that are produced and organised by the cells. If this all seems a bit abstract, think of a bowl of jelly: that’s pretty much the stuff I’m talking about (the jelly more so than the bowl).

So when we talk about skin growing, we’re talking about more cells and more matrix. Cells divide and spit out a bunch more matrix such as collagen. The tricky bit is that they have to do this while still doing their job of holding together a tight seal against the outside world. Can you imagine how hard it would be to make a bridge longer while there are cars driving over it?

We still have a lot to learn about how this works, but surgeons have been putting the idea of mechanically-driven growth to work for a few decades now. Lengthening a bone was first attempted (as far as we know) in 1905 by Italian surgeon, Alessandro Codavilla, and the current method, known as distraction osteogenesis (used, for example, to replace large amounts of bone smashed by an accident), was pioneered in theUSSR by Gavriil Ilizarov in the 1940s or ’50s. Distraction osteogenesis involves letting the fracture (or cut) begin healing, but before it gets too far, to slowly move the two bone fragments apart – a rate somewhere around 1mm a day, if I remember rightly. The current procedure is reportedly painful enough, but I read that Codavilla tried to do the expansion all in one hit! Bone has not been the only target tissue. Also in the 1950s, Charles Neuman implanted a balloon beneath the skin to cause expansion as it was gradually inflated. Both of these methods have become widely used since the 1980s.

The great thing about skin expansion is that it lets the surgeon use the patient’s own skin to cover up defects, so you get the right amount of skin, it’s alive and fully functional already and won’t be rejected by the immune system. It’s challenging, though, for both clinician and patient: it’s hard to know exactly what size and shape of expander you need and how much to inflate it (because the elasticity of skin means it will shrink once the extra tension is removed), and the patient has to put up with having a huge bubble under their skin for a few weeks. But it works beautifully.

Getting back to how… Both the matrix and the cells of skin are under constant tension, like the rubber of an inflated balloon. Skin has to be pretty flexible to let us move, but once it’s stretched past this normal range of movement, the cells have to get busy to avoid the skin breaking.

There are a few different ways by which cells detect stretch, and that’s probably getting a bit too technical. But the effects on the cell are basically these: the cell gets set to divide (the process is called mitosis, and results in one cell becoming two of the same), it produces more extracellular matrix like collagen, and it gives out signals to encourage other cells around it to do the same. Not all of this goes on in any one cell at one time, but the end effect is, as mentioned above, more cells and more matrix. In the outer layer (the epidermis), we need more cells to cover the increasing surface area. Beneath this (in the dermis), we need more cells to build and maintain the tissue, and they need more matrix to hang on to and to carry the load.

To divide, a cell has to first detach from its surroundings and shrink back into a ball. So when a tissue grows, only a small proportion of its cells can divide, while the others go on holding everything in place. Likewise, when new matrix is produced, the existing structure needs to be disrupted somewhat to jostle it into place. It’s these processes that particularly fascinate me at present. I hope to have a lot more to tell you about them in the coming months!

 

An interesting aside: cells divide along the line of maximum tension. This is handy for skin growth, because it means a cell doubles in the direction of stretch. But the cartilage of growing bones is under a compressive load – that is, it’s being pushed rather than pulled. When you squeeze something elastic, you’ll notice it spreads out to the sides. So when the cartilage in the growth plate gets compressed, the cells are stretched sideways, which means they also divide sideways. For the bone to get longer, then, the newly divided cells have to do a little tumble so they’re both lined up with the axis of the bone (and load).

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