Garcia Manyes lab Single Molecule Mechanobiology Laboratory

Diagram of a protein contracting and expanding

We are fascinated by how mechanical forces travel across the cell and cause biochemical changes inside the nucleus, directly affecting cell behaviour. To understand the molecular mechanisms underlying these processes, we combine new techniques to apply controlled forces at the individual chemical bond, protein and cell levels.  

Cells are continuously exposed to mechanical perturbations from the environment, neighbouring cells and fluids moving around them. While some of these mechanical inputs are sensed and remain at the cell surface, others can travel long distances inside the cell to reach the nucleus, the cell’s decision hub, and influence cell behaviour. In fact, mechanical forces determine many basic cell functions, and are related to diseases like cardiovascular conditions or cancer. 

These processes are often controlled by the elastic properties of the individual proteins, which need to constantly stretch and recoil under a load. However, many of the scientific methods commonly used in molecular and cell biology cannot apply and monitor the effects of forces.

My laboratory develops and applies single molecule techniques to capture the individual unfolding and refolding trajectories of proteins under force. Borrowing concepts from polymer physics, protein chemistry and molecular biology, we aim to understand the molecular basis of protein elasticity.

Arguably the main challenge in our field is seeing whether phenomena observed in single-molecule experiments translate to cells. Specifically, we do not know whether individual molecules working inside the cell respond to force according to the same fundamental physical laws that we see in the single-molecule experiments. Closing this gap has become an urgent question in mechanobiology.