A Mechanical Basis for Memory

It’s not a huge jump to imagine that the brain functions like a computer – especially as artificial intelligence makes its way into every aspect of modern life. But what could this idea really look like on a molecular level? A bold theory suggests that a protein called talin might hold the answer.

Talin is found in all cells and connects the cytoskeleton inside the cell to the plasma membrane surrounding it. The synapses in your brain – the structures that allow brain cells to communicate with one another – contain scaffolds made of talin molecules. Talin can switch between two shapes, known as conformations. Researchers studying talin have suggested that the brain could work like a mechanical computer written in binary code, with folded and unfolded talin molecules acting as the ‘0s’ and ‘1s.’

This idea is known as the MeshCODE theory, named after the interlinked scaffolds of synaptic talin molecules known as ‘meshwork.’ The MeshCODE theory was first introduced in 2021 by a team of researchers led by Dr. Ben Goult at the University of Liverpool.  According to the theory, the electrical signals passing through the brain change the pattens of ‘0s’ and ‘1s’ in long chains of talin molecules, offering an explanation for how memories are physically stored in the brain, like how the transistors in a computer store data.  

Cytoskeleton: A large network of interlinking protein fibres and other molecules that gives cells their structure.

Conformation: Any of the arrangements in which the atoms in a specific molecule can organise themselves.

It’s a fantastic theory with huge implications for our understanding of consciousness – but does it hold up in real human biology? And how exactly would one go about testing it? To test the feasibility of the MeshCODE theory, the Goult lab collaborated with researchers at the Pasteur Institute of Lille specialising in a disease infamous for its devastating effects on memory: Alzheimer’s. In Alzheimer’s disease, a key protein called amyloid precursor protein (APP) is abnormally processed, causing toxic molecules called amyloid beta peptides to accumulate. When these peptides build up, they trigger inflammation and lead to the death of brain cells.

The researchers searched for which proteins in the body interact with APP and affect the way it’s processed and found that talin was a prime candidate. After a series of careful experiments, they arrived at the following scenario: in a healthy brain, the APP outside of brain cells and the talin inside the cells connect to form a bridge across the synapse. The links between APP and talin are crucial for the mechanical memory in brain cells, keeping the cells on either side of the synapse synchronised. However, in Alzheimer’s, abnormal changes in APP mess with the bridge’s structural integrity, causing the series of ‘0’ and ‘1’ talin conformations extending into the cell to be lost. If the string of talin shapes is what’s responsible for encoding memories, this could explain the memory loss that happens in Alzheimer’s. 

The Goult lab has published a six-part hypothesis on the interactions between talin and APP that will guide their next few years of research. Time will tell if a mechanical basis for memory and consciousness is more than just a theory.

Journal references:

C. Ellis et al., The structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer’s disease. Open Biology. 2024.

Goult BT. The Mechanical Basis of Memory - the MeshCODE Theory. Front Mol Neurosci. 2021.