RESEARCH
Every tissue is an ever-changing landscape.
Cells shape tissues. Tissues shape cells.
A tissue is not a uniform backdrop for its cells. Each cell occupies a local mechanical environment and metabolic state, shaped by factors including tension, compression, crowding, nutrient availability and energy demand.
These conditions can influence whether a cell grows, divides, dies, moves or changes shape. In turn, each of these behaviours redistributes forces, consumes resources and changes the environment experienced by neighbouring cells.
Force and energy are not separate stories.
Mechanical forces and metabolic states are often studied separately, but in living tissues they are inseparable. Generating force, moving, growing and changing shape consume energy and molecular resources. Meanwhile, tension, compression and crowding can alter energy demand, nutrient use and metabolic state.
This creates a reciprocal relationship: metabolism helps determine the mechanical work a cell can perform, while mechanical conditions reshape its metabolic needs and capabilities. We test whether this coupling connects the conditions experienced by individual cells to the coordinated behaviour of the tissue.
One tissue. Two landscapes.
One experiment.
Two readouts.
We measure mechanical and metabolic states in the same living tissue, at the same time and at single-cell resolution. This allows us to map how both landscapes vary across a tissue, and to follow what individual cells do as those conditions change.
We then connect each cell’s local environment to its subsequent behaviour: whether it grows, divides, dies, moves or changes shape. By perturbing one side of the relationship and measuring the other, we can test whether mechanical–metabolic coupling merely accompanies cell behaviour or actively helps to determine it.
From observation to causation.
Measuring mechanics and metabolism together reveals how their states change across a tissue. We then perturb one landscape and measure how the other responds, allowing us to determine the direction, timing and strength of their reciprocal influence.
We use complementary approaches to reshape the mechanical environment: dynamically stiffening or softening MeHA hydrogels, applying tissue stretch and using micropatterning to redistribute forces across groups of cells. In parallel, we alter nutrient availability and metabolic pathways while continuing to image forces, metabolites and cell behaviours.
By changing each side of the relationship in turn, we can uncover how mechanics reshapes metabolism, and how metabolism alters the mechanical work cells can perform.
How tissues are made.
And unmade.
Development, repair and disease emerge from the accumulated behaviours of many individual cells. When mechanical and metabolic conditions coordinate those behaviours, tissues can form, adapt and maintain their function. When that relationship is disrupted, the same cellular decisions can instead drive disorganisation and disease.
By uncovering how mechanics and metabolism act together across scales, we aim to discover the principles that connect individual cell behaviour to the formation, maintenance and breakdown of living tissues.