Building a working brain depends on complex interactions between nerve cells and their environment. Now, cutting-edge tools from both biology and physics are helping us understand how physical factors shape brain development.
How do you grow a brain?
We need to ask this question to understand how our brains work in normal life, and also how to combat disease when things go wrong. The answer lies right at the beginning of life, in the developing embryo, which is where nerve cells – the building blocks of our brain and nervous system – are first born.
To build a brain from scratch, the newly born nerve cells send out long protrusions, called axons, which grow towards cells elsewhere in the body. The axons are the body’s electrical cables, helping cells within the brain and nervous system communicate. As the axons grow, they follow well-defined paths and encounter different environments. This is like us following a route through a city: sometimes we have to go around roadblocks, and sometimes we walk on hard pavements or soft grass. The difference between us and an axon, though, is that we can see where we are going; but how does a small part of a growing cell manage to find its way through the body?
The answer is a sensitive structure called the growth cone. This is found at the end of each growing axon and resembles a microscopic hand, which moves around constantly as it samples its environment. Neuroscientists already know that growth cones sense chemicals produced by other cells; however, we also know that they temporarily stick to the surface they grow along and ‘grasp’ it as they move forward.
It’s now thought that growth cones pull themselves along, just as you or I might pull ourselves up with our hands when climbing, which in turn allows axons to lengthen. If the axon’s ‘hand’ pulls on its substrate, it makes sense that the substrate’s mechanical properties – such as stiffness or how rough the surface is – could affect how axons navigate towards their targets. (Think of climbing a mountain made of soft jelly: this would be impossible, but rock is no problem because we can work up enough force on a hard surface to move upwards.)
Biologists are now starting to understand how this works, using sophisticated experimental tools that combine the best of biology and physics. For example, we can now calculate exactly how strongly growth cones pull, simply by putting nerve cells on a flexible surface with tiny labelled beads embedded in it and imaging the lot with a powerful microscope. As the growth cones pull, they distort the surface and displace the beads. How far the beads move depends on how much force is applied to the surface.
Another useful tool, recently borrowed from nanotechnology and materials science, is the atomic force microscope. This is basically an extension of our sense of touch: it consists of a nano-scale probe, which acts like a ‘fingertip’ that can poke single cells. A 2009 study, published in the Biophysical Journal, used the atomic force microscope to prod the ends of growing axons. When the axons hit this ‘roadblock’, they promptly drew back and grew in a different direction, showing that nerve cells adjust their behaviour to suit their physical environment.
Thanks to these advances, we now know more than ever before about the factors and processes that shape brain development. We are still a long way from growing brain tissue in a dish, but we can definitely say that brains are wired on physics as well as on chemistry.
Growth cones pulling – Betz et al. (2011) Growth cones as soft and weak force generators, PNAS 108, 13420–13425 – open access
Poking growth cones – Franze et al. (2009) Neurite Branch Retraction Is Caused by a Threshold-Dependent Mechanical Impact, Biophysical Journal 97, 1883–1890 – behind paywall