Integrative cell and tissue dynamics

We aim at understanding how physical forces and molecular control modules cooperate to drive biological function.

We develop new technologies to map and perturb the main physical properties that determine how cells and tissues grow, move, invade and remodel.

By combining this physical information with systematic molecular perturbations and computational models we explore the principles that govern the interplay between chemical and physical cues in living tissues.
We study how these principles are regulated in physiology and development, and how they are derailed in cancer and aging.

Making cellular forces visible

To study cell and tissue dynamics we develop new technologies to measure physical forces at the cell-cell and cell-matrix interface. By combining these technologies with computational analysis of cell shape and velocity we obtain a full experimental characterization of epithelial dynamics during tissue growth, wound healing and cancer cell invasion.

Tumour invasion by stromal forces

Cancer cell invasion and metastasis remain the leading cause of death in patients with cancer. Both processes are the result of a complex interaction between tumor cells and their microenvironment. One of our main lines of research is to study how tumours exploit the functions of non-cancer cells in their microenvironment to invade and metastasize. We focus on the interaction between epithelial cancer cells and Cancer Associated Fibroblasts (CAFs), the most abundant cell type in the tumour stroma.

Optogenetics to control cell mechanics

The recent development of optogenetic technologies offers promising possibilities to control signalling pathways with high spatiotemporal resolution. By expressing genetically encoded light-sensitive proteins, optogenetic technology enables the reversible perturbation of intracellular biochemistry with subcellular resolution. We have developed optogenetic tools based on controlling the activity of endogenous RhoA to upregulate or downregulate cell contractility and to control cell shape and mechanotransduction.

Collective durotaxis: a mechanism for cellular guidance by mechanical cues

Directed cell migration is one of the earliest observations in cell biology, dating back to the late XIX century. Also known as taxis, directed cell migration has been commonly associated with chemotaxis, i.e. the ability of a broad variety of cell types to migrate following gradients of chemical factors. We recently demonstrated a new mode of collective cell guidance by mechanical cues, called collective durotaxis. This new migration mode emerges only in cell collectives and, strikingly, does not require isolated cells to exhibit gradient sensing.

Organoid mechanobiology

Organoids are large multicellular structures that self-organize in vitro and maintain a similar organization and functionality than the organ from which they are derived. Organoids from many organs have now been obtained from embryonic stem cells, induced pluripotent stem cells and organ progenitors. We use intestinal and kidney organoids to study how epithelia adopt three-dimensional shapes that closely resemble their structure in vivo. We also use organoids grown from primary tumors to understand how epithelial structure and function are lost with disease progression.

Engineering epithelial shape and mechanics from the bottom up

We develop new approaches to engineer epithelia in 3D. Using these approaches, we study the principles that govern the emergence of tissue shape from the bottom up. We recently found that epithelial sheets can stretch up to four times their initial area without breaking, and that they are able to recover their initial size in a fully reversible way when unstretched. Surprisingly, some cells in the tissue barely stretch, while others become ‘superstretched’, increasing their area more than ten times. We call this phenomenon ‘active superelasticity’.