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.
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’.
|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|
|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|
|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|
|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|
- Soft Lithography
- Micro/Nano fabrication
- Cell stretching
- Live Confocal Microcopy
- Magnetic Tweezers
- Magnetic Twisting Cytometry
- Monolayer stress microscopy
- Traction microscopy
- 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
This week, the conference organised by the Institute for Bioengineering of Catalonia (IBEC) and the European Molecular Biology Laboratory (EMBL) brought together a total of 200 international experts in the field of bioengineering at La Pedrera building in Barcelona. At the opening of the event, which was led by the mayor of Barcelona, Ada Colau, attention was drawn to Barcelona’s consolidation as an international centre of research and knowledge.
Three IBEC projects have been selected to receive funding from “La Marató 2018: Against Cancer.” One of the projects is led by the researcher Pere Roca-Cusachs and the other two are co-led by the researchers Xavier Trepat and Núria Montserrat. The awarding ceremony took place on October 30 in the Auditorium of the Academy of Medical and Health Sciences of Catalonia and the Balearic Islands. In this edition, over the 188 evaluated projects, 43 have been selected by an international committee of experts in cancer based on their excellence, methodology and relevance. La Marató de TV3, together with Catalunya Ràdio, broadcasts its annual telethon to raise funds for scientific research into various diseases with a different theme each year.
Great success of the Mechanobiology of Cancer Summer School 2019 organised by the Mechano·Control project
More than 60 people attended the “Mechanobiology of Cancer Summer School 2019” organised by IBEC as the center is in charge of coordinating the Mechano·contorl project. The summer school was held in Prullans, a tiny village located at the Catalan Pyrinees between 17 and 21 of September. The event was a great success both in participation and scientific level. The aim of the summer school was to provide training on mechanobiology, and specifically its application to breast cancer, and promote interactions between professionals of the field. The school included lectures as well as practical workshops in different techniques and disciplines, ranging from modelling to biomechanics to cancer biology. The Mechano·Control project, coordinated by Pere Roca-Cusachs, principal investigator of the IBEC is the largest European project coordinated by the IBEC to date.
A research team led by the IBEC, in collaboration with the CMR [B], discovers a mechanism that generates binucleated cells.This mechanism has been identified during the regeneration of the heart of the zebrafish, and could be associated with the extraordinary regenerative power of this animal. After an acute heart lesion, such as a myocardial infarction, the human heart is unable to regenerate. The adult cardiac cells cannot grow and divide to replace the damaged ones, and the lesion becomes irreversible. But this does not happen in all animals. A freshwater fish native to Southeast Asia, known as a zebrafish, can completely regenerate its heart even after 20% ventricular amputation.
The President of the European Research Council, Jean-Pierre Bourguignon, visited last May 15th the Institute for Bioengineering of Catalonia (IBEC). The event was inaugurated by IBEC’s Director, Josep Samitier, who presented an overview on the cutting-edge research carried out at the institute in the fields of bioengineering and nanomedicine. Afterwards, ERC Grantees working at IBEC had the opportunity to explain the impact of ERC grants on their professional careers and established a dialogue with ERC President on the past, present and future of the European Research Council.
The MECHANO·CONTROL consortium, led by several research institutions across Europe, is launching a Summer School that will be taking place between 17-20 of September 2019 at the Eco Resort in La Cerdanya. The aim of the summer school is to provide training on mechanobiology, and specifically its application to breast cancer.This school will include lectures as well as practical workshops in different techniques and disciplines, ranging from modelling to biomechanics to cancer biology. There will be scientific sessions in the morning, mixing 6 keynote speakers with 18 short talks selected from abstract submissions by junior scientists attending the school. In the afternoon, there will be 2-3-hour practical workshops, given by scientists from the MECHANO·CONTROL consortium. The course will also include leisure activities.
Cell migration is an essential biological process that drives tissue and organ formation during embryo development, and also helps protect the body through immune response and wound healing mechanisms. The shape changes necessary for cell migration depends on dynamic organization and force generation from the cell’s internal actomyosin cytoskeleton, which is made up of structural actin filaments and contractile myosin motor proteins. Reorganization of these components enables two mechanisms of cell migration.
An opinion piece by IBEC group leader Xavier Trepat has appeared in the News and Views section of the current issue of Nature, which is devoted to ‘Bottom-up biology’. In his piece ‘Bottom does not explain top’, Xavier argues that understanding how complex biological structures – or even entire cells – are built can only provide a certain amount of insight into how biological systems function at higher levels of organization. There are many variables such as density, or even pathologies suffered by the subject, that affect cell behavior at the mesoscale – that is, at the longer, more ‘system-level’ scale than that of the individual components of an organism. Cells in a group, for example, can sense or respond to external stimuli that an individual cell cannot identify.
Wednesday’s press release about the Nature paper published by IBEC and UPC researchers got a lot of press coverage.
One of the most enviable features of superheroes is their ability to stretch their bodies beyond imaginable limits. In a study published today in Nature, scientists have discovered that our cells can do just that. With every beat of the heart and every breath into the lungs, cells in our body are routinely subjected to extreme stretching. This stretching is even more pronounced when cells shape our organs at the embryo stage, and when they invade tissues through narrow pores during cancer metastasis – but how cells undergo such large deformations without breaking has remained a mystery until now.