About
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’.
Staff
Xavier Trepat
ibecbarcelona.euProjects
| NATIONAL PROJECTS | FINANCER | PI |
|---|---|---|
| mGRADIENTMecanobiología de la migración colectiva durante la haptotaxis y la durotaxis: aplicación a los organoides intestinales (2019-2022) | MICIU Generación Conocimiento: Proyectos I+D | Xavier Trepat |
| DYNAGELHidrogeles biocompatibles con rigidez dinámicamente ajustable para estudiar la mecanobiología de células y tejidos (2019-2022) | MICIU Retos investigación: Proyectos I+D | Raimon Sunyer |
| INTERNATIONAL PROJECTS | FINANCER | PI |
|---|---|---|
| EpiFold Engineering epithelial shape and mechanics: from synthetic morphogenesis to biohybrid devices (2021-2025) | European Commission, ERC-AdG | Xavier Trepat |
| The role of intermediate filaments in stress resistance in 3D epithelial structures (2021-2023) | Deutsche Forschungsgemeinschaft (DFG), Walter Benjamin-Programme | Tom Golde |
| Mechano·Control Mechanical control of biological function (2017-2022) | European Commission, FET Proactive | Xavier Trepat |
| Control of cell collective flows and tissue folding by means of surface patterns (2021-2022) | Human Frontier Science Program, HFSP Beca postdoctoral | Pau Guillamat |
| PRIVATELY-FUNDED PROJECTS | FINANCER | PI |
|---|---|---|
| Mech4Cancer · Enabling technologies to map nuclear mechanosensing: from organoids to tumors (2020-2023) | Obra Social La Caixa: Health Research Call | Xavier Trepat |
| T cell exclusion during cancer immune evasion and immunotherapy failure: cell types, transcriptional programs and biomechanics (2020-2023) | Fundació La Marató de TV3 | Xavier Trepat |
| Joint Programme Healthy Ageing | Obra Social La Caixa | Xavier Trepat |
| Understanding and measuring mechanical tumor properties to improve cancer diagnosis, treatment, and survival: Application to liquid biopsies (2017-2022) | Obra Social La Caixa | Xavier Trepat |
| FINISHED PROJECTS | FINANCER | PI |
|---|---|---|
| OPTOLEADER Optogenetic control of leader cell mechanobiology during collective cell migration (2019-2021) | European Commission, MARIE CURIE – IF | Leone Rossetti |
| MECHANOIDS Probing and controlling the three-dimensional organoid mechanobiology (2019-2021) | European Commission, MARIE CURIE – IF | Manuel Gómez |
| TensionControl Multiscale regulation of epithelial tension (2015-2020) | European Commission, ERC – CoG | Xavier Trepat |
| El mecanoma de la adhesión epitelial: mecanismos de detección, resistencia y transmisión de fuerzas intercelulares | MINECO, I+D-Investigación fundamental no orientada | Xavier Trepat |
| MICROGRADIENTPAGE Micro Gradient Polyacrylamide Gels for High Throughput Electrophoresis Analysis | European Commission, ERC-PoC | Xavier Trepat |
| GENESFORCEMOTION Physical Forces Driving Collective Cell Migration: from Genes to Mechanism | European Commission, ERC-StG | Xavier Trepat |
| CAMVAS Coordination and migration of cells during 3D Vasculogenesis (2014-2017) | European Commission, MARIE CURIE – IOF | Xavier Trepat |
| DUROTAXIS Mecanobiología de la durotaxis: de las células aisladas a los tejidos | MINECO, Proyectos I+D Excelencia | Xavier Trepat |
Publications
Equipment
- Soft Lithography
- Micro/Nano fabrication
- Cell stretching
- Live Confocal Microcopy
- Magnetic Tweezers
- Magnetic Twisting Cytometry
- Monolayer stress microscopy
- Traction microscopy
Collaborations
- Julien Colombelli / Eduard Batlle
Institute for Research in Biomedicine (IRB) Barcelona - Marino Arroyo
Universitat Politècnica de Catalunya, Barcelona - Guillaume Charras / Roberto Mayor
University College London, UK - Erik Sahai
Cancer Research, UK - Benoit Ladoux
Université Paris 7, France - Jim Butler & Jeff Fredberg
Harvard University, Boston - Danijela Vignjevic
Institut Curie, Paris - Jonel Trebicka
Department of Internal Medicine I, University Hospital Frankfurt
News
The intestinal organoids hit the media
The group led by Xavier Trepat at IBEC, together with Marino Arroyo, associate researcher at IBEC, and other international collaborators have developed intestinal organoids and measured cellular forces in order to decipher how the inner wall of this vital organ folds and moves.
Researchers discover how the intestinal epithelium folds and moves by measuring its forces
An international team led by Xavier Trepat at IBEC, with support from “La Caixa Foundation, measures the cellular forces in mini-intestines grown in the laboratory, deciphering how the inner wall of this vital organ folds and moves.
Mechanical forces, half of the alphabet to understand life
Xavier Trepat and international experts remind us in a piece published in the Journal Nature by science writer Amber Dance, the crucial role of physics in order to understand biological entities such cells and organs, both in health and disease. In words of Trepat: “Understanding a cell without physics is like trying to write a book with only half the letters of the alphabet”.
The study of physical forces in tumor progression
Xavier Trepat, leader of the IBEC “Integrative cell and tissue dynamics” group, is interviewed for the Big Vang section of La Vanguardia expaining his study to improve the diagnosis of tumor progression disease and to develop new drugs.
Bioengineering against cancer
Xavier Trepat and Pere Roca-Cusachs, group leaders at IBEC, appear on the journal “ABC” explaining their research project that they will carry out thanks to funding from “la Caixa” as part of the «Health Research Call ».
Bioengineering against cancer: IBEC researchers receive funding from La Caixa
IBEC researchers Elena Martínez, Xavier Trepat and Pere Roca-Cusachs aim to understand the processes that promote metastasis in colorectal cancer using innovative bioengineering tools, such as bioprinting and microscopy capable of revealing forces at the cellular level. The results will be translated into a device that will recreate the tumor environment from cancer cells derived from patients, as well as a new technology that will allow to visualize how physical forces affect the nuclei of metastatic cells.
How can we measure mechanical stress in living tissues?
A team of experts from the Institute for Bioengineering of Catalonia (IBEC) has published a review in the journal Nature Reviews Physics detailing the different techniques used to calculate mechanical stress in tissues, both in cell cultures and in vivo. Determining these mechanisms of mechanical stress is crucial to study processes linked to morphogenesis, homeostasis, and diseases such as cancer. In order to work properly, living tissues need to continuously move, divide, reshape and perceive their microenvironment. In other words, they need to withstand certain mechanical stress derived from contact.
IBEC researchers explain “Durotaxis”, a cell migration mechanism with a potential role in several diseases
Xavier Trepat, group leader of the “Integrative cell and tissue dynamics” at IBEC together with Raimon Sunyer, Senior researcher in Trepat’s lab, have written a Primer in Current Biology magazine on “Durotaxis”, a cell migration mechanism that might have a role in several disease states that include the stiffening of tissues. Embryo development, tumour progression or the immune response against pathogens requires cell migration.
The European Research Council awards funding to 10 projects in Catalonia
Several media channels have reported this year’s European Research Council grants to various projects being undertaken in Catalonia. Among these projects is that of Xavier Trepat, group leader at IBEC.
Xavier Trepat receives the ERC Advanced Grant to lay the basis of a new generation of biological robots
The researcher at the Institute for Bioengineering of Catalonia (IBEC), Xavier Trepat, has received the prestigious ERC Advanced Grant awarded by the European Research Council (ERC) worth 2.5 million euros. Thanks to this grant the expert and his group will be able to study the mechanical properties of the epithelium in 3D and to lay the foundations for a pioneering technology called “Epifluidics”, which will allow the design of biological robots.