A team of researchers at the University of Liverpool, working in collaboration with the Mechanobiology Institute at the National University of Singapore, has made a significant breakthrough in understanding how cells sense and respond to physical forces. Their latest study reveals that vinculin - a protein long considered a passive adapter - plays an active role in mechanical signalling and cellular memory.
For decades, vinculin was thought to serve primarily as a structural link between adhesion complexes and the cytoskeleton. However, this new research demonstrates that vinculin contains six force-dependent binary switches, similar to those previously discovered in the protein talin. These switches open and close in response to mechanical stress, allowing cells to encode and retain information - a concept the researchers describe as mechanical memory.
Using single-molecule magnetic tweezers, the team was able to pull on individual vinculin molecules and characterise each of the six switches. This detailed analysis marks a paradigm shift in mechanobiology, expanding the understanding of how cells process mechanical signals.
Professor Ben Goult, Mechanistic Cell Biology, University of Liverpool said: "Our discovery that vinculin is mechanically active opens up a new area of research. These switches suggest that vinculin is not just a structural component, but a dynamic participant in cellular decision-making. It's a fundamental change in how we view this protein."
The implications of this work are far-reaching. In the heart, mutations in vinculin are known to cause dilated cardiomyopathy and heart failure. Re-evaluating these mutations in the context of vinculin's mechanical switches could lead to improved understanding of disease mechanisms and potential therapeutic targets.
The study also lays the groundwork for future investigations into vinculin's role in the brain. Talin and vinculin together form a meshwork of binary switches - referred to as the MeshCODE -which may be involved in processing and storing mechanical and chemical information in neurons. Researchers are now exploring vinculin's function in synaptic activity through collaborations with the Liverpool Interdisciplinary Neuroscience Centre (LINC) and the University of Helsinki.
While the current findings are based on in vitro experiments, the team is actively studying vinculin in living cells and engineered heart tissues. They are also working with the University of Liverpool's Centre for Proteome Research to examine vinculin's interactions and post-translational modifications during cell migration.
Professor Goult conclude: "This is an exciting time for mechanobiology. We're beginning to see how mechanical forces shape cellular behaviour in ways we hadn't imagined. Vinculin's switches may be the key to unlocking how cells remember and respond to their physical environment."
The paper 'The mechanical response of vinculin' was published in Science Advances (DOI:10.1126/sciadv.ady6949).
