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Sunday, July 14, 2013

Nanoscale communication

What would it be like to occupy the cities inside cells? Imagine if we could peer inside cells and watch the tiny proteins go about their daily lives. We'd see the tradesmen hard at work building structures and taking them down again in response to the changing needs. We'd see personalised taxi drivers and hoards of buses transporting goods to other regions, doctors and nurses fixing damage, and factory workers busily pumping out energy for the whole city. These tiny proteins must communicate with each other for the cell to work efficiently as a whole.

Unfortunately we can't peer inside cells with this much detail. Using a standard confocal microscope available to most scientists, we can see major structures inside a cell. This is perhaps equivalent to looking at large factory buildings using a telescope from the international space station. These protein doctors and factory workers are hidden from our view, inside the blur that marks the limit of resolution. So scientists must use creative technologies to infer where these proteins are and how they function, rather than directly watching their actions.

In the last 5 years, new imaging techniques have allowed us to see beyond these major structures and peer inside these large-scale factories. One really great example of this technology is 'Super Resolution Imaging of Chemical Synapses in the Brain', published in 2010 in the scientific journal 'Neuron'. These authors use a new imaging technique known as STORM to see up to 10 times more detail than is possible with a typical confocal microscope.
The presynaptic neuron communicates with the postsynaptic neuron by releasing neurotransmitter than diffuses across the synaptic cleft.

Synapses are the parts of neurons that talk to each other---the ultimate example of cell communication. The presynaptic neuron releases molecules of neurotransmittor that diffuse across the synaptic cleft and bind the postsynaptic neuron, which responses appropriately according to the messages received. Synapses are where all the action is at, where memories are formed and strengthened, and where learning takes place. Unfortunately for people with debilitating diseases such as Alzheimer's or Autism, their synapses do not function as they should.

The synapses are very small, at only half a micron, or 1/2000th of a millimetre across. This is beyond the capabilities of our confocal microscopes, making it difficult for scientists to study these synapses. But thanks to super resolution imaging, we can now zoom in just a little bit more on these tiny cellular cities and see what's going on in a normal cell, or what's going wrong in a diseased cell.

Dani 2010 synapse
Dani, A., Huang, B., Bergan, J., Dulac, C., & Zhuang, X. (2010). Superresolution Imaging of Chemical Synapses in the Brain. Neuron, 68(5), 843–856. doi:10.1016/j.neuron.2010.11.021. (Figure 1)

With confocal imaging (left), the synapse is blurred and unstructured. We cannot see the details of the two neurons synapsing onto each other, and we cannot make out the synaptic cleft that we know must be there. In comparison, using super resolution STORM imaging (right), we can now make up the details of the synapse. The green and red colours show two different neurons, talking to each other across the synaptic cleft that lies in between.

Here we are looking at nanoscale communication taking place. Imagine what cellular secrets we would find if we could see deeper into cells...

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