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Integrative cell and tissue dynamics

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

Projects

NATIONAL PROJECTSFINANCERPI
mGRADIENTMecanobiología de la migración colectiva durante la haptotaxis y la durotaxis: aplicación a los organoides intestinales (2019-2022)MICIU Generación Conocimiento: Proyectos I+DXavier Trepat
DYNAGELHidrogeles biocompatibles con rigidez dinámicamente ajustable para estudiar la mecanobiología de células y tejidos (2019-2022)MICIU Retos investigación: Proyectos I+DRaimon Sunyer
INTERNATIONAL PROJECTSFINANCERPI
EpiFold Engineering epithelial shape and mechanics: from synthetic morphogenesis to biohybrid devices (2021-2025)European Commission, ERC-AdGXavier 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 ProactiveXavier 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 PROJECTSFINANCERPI
Mech4Cancer · Enabling technologies to map nuclear mechanosensing: from organoids to tumors (2020-2023)Obra Social La Caixa: Health Research CallXavier Trepat
T cell exclusion during cancer immune evasion and immunotherapy failure: cell types, transcriptional programs and biomechanics (2020-2023)Fundació La Marató de TV3Xavier Trepat
Joint Programme Healthy AgeingObra Social La CaixaXavier Trepat
Understanding and measuring mechanical tumor properties to improve cancer diagnosis, treatment, and survival: Application to liquid biopsies (2017-2022)Obra Social La CaixaXavier Trepat
FINISHED PROJECTSFINANCERPI
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 – CoGXavier Trepat
El mecanoma de la adhesión epitelial: mecanismos de detección, resistencia y transmisión de fuerzas intercelularesMINECO, I+D-Investigación fundamental no orientadaXavier Trepat
MICROGRADIENTPAGE Micro Gradient Polyacrylamide Gels for High Throughput Electrophoresis AnalysisEuropean Commission, ERC-PoCXavier Trepat
GENESFORCEMOTION Physical Forces Driving Collective Cell Migration: from Genes to MechanismEuropean Commission, ERC-StGXavier Trepat
CAMVAS Coordination and migration of cells during 3D Vasculogenesis (2014-2017)European Commission, MARIE CURIE – IOFXavier Trepat
DUROTAXIS Mecanobiología de la durotaxis: de las células aisladas a los tejidosMINECO, Proyectos I+D ExcelenciaXavier 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

Alberto Elosegui-Artola, Xavier Trepat and Pere Roca-Cusachs’ paper in Trends in Cell Biology has made the cover of the latest issue of the Cell-family journal. In ‘Control of Mechanotransduction by Molecular Clutch Dynamics’, the IBEC researchers review how cell dynamics and mechanotransduction are driven by molecular clutch dynamics. The molecular clutch hypothesis suggests a mechanism of coupling between integrins and actin during cell migration, whereby a series of bonds that dynamically engage and disengage link cells to their microenvironment.

IBEC research on cover of Trends

Alberto Elosegui-Artola, Xavier Trepat and Pere Roca-Cusachs’ paper in Trends in Cell Biology has made the cover of the latest issue of the Cell-family journal. In ‘Control of Mechanotransduction by Molecular Clutch Dynamics’, the IBEC researchers review how cell dynamics and mechanotransduction are driven by molecular clutch dynamics. The molecular clutch hypothesis suggests a mechanism of coupling between integrins and actin during cell migration, whereby a series of bonds that dynamically engage and disengage link cells to their microenvironment.

Researchers have shown for the first time that ion channels that are capable of detecting changes in the physical properties of the cellular environment play a key role in tumor invasion and metastasis. The discovery, led by led by Miguel Angel Valverde from the Department of Experimental and Health Sciences of the UPF and involving IBEC’s Integrative Cell and Tissue Dynamics group, could open new avenues in the development of new drugs that reduce the risk of metastasis.

Shedding light on metastasis in the brain

Researchers have shown for the first time that ion channels that are capable of detecting changes in the physical properties of the cellular environment play a key role in tumor invasion and metastasis. The discovery, led by led by Miguel Angel Valverde from the Department of Experimental and Health Sciences of the UPF and involving IBEC’s Integrative Cell and Tissue Dynamics group, could open new avenues in the development of new drugs that reduce the risk of metastasis.

The way cells find their way around is by ‘groping’ rather than seeing their surroundings: this is the main conclusion of a study published in Nature last week involving several IBEC groups and their collaborators. “We determined how cells detect the position of molecules (or ligands) in their environment with nanometric accuracy,” explains Pere Roca-Cusachs, group leader at IBEC and assistant professor at the University of Barcelona, who led the study. “By adhering to the ligands, the cells apply a force they can detect. As this force depends on the spatial distribution of the ligands, this allows the cells to ‘feel’ their surroundings. It’s like recognizing somebody’s face in the dark by touching it with your hand, rather than seeing the person.”

Cells feel their environment to explore it

The way cells find their way around is by ‘groping’ rather than seeing their surroundings: this is the main conclusion of a study published in Nature last week involving several IBEC groups and their collaborators. “We determined how cells detect the position of molecules (or ligands) in their environment with nanometric accuracy,” explains Pere Roca-Cusachs, group leader at IBEC and assistant professor at the University of Barcelona, who led the study. “By adhering to the ligands, the cells apply a force they can detect. As this force depends on the spatial distribution of the ligands, this allows the cells to ‘feel’ their surroundings. It’s like recognizing somebody’s face in the dark by touching it with your hand, rather than seeing the person.”

Researchers at the Institute for Bioengineering of Catalonia (IBEC) have observed, for the first time, mechanical waves that form after collisions between cellular tissues. After a collision, cells are pushed and deformed into waves that travel at a speed of three millimeters a day. This unexpected behavior defies what we know about cellular dynamics, and could be relevant to understand embryonic development or metastasis. Mechanical waves – such as seismic waves, sound, or waves in the sea – are a phenomenon easily explained by the laws of physics: when two particles collide, a wave travels through the surrounding material.

Cell collisions reveal a new type of wave

Researchers at the Institute for Bioengineering of Catalonia (IBEC) have observed, for the first time, mechanical waves that form after collisions between cellular tissues. After a collision, cells are pushed and deformed into waves that travel at a speed of three millimeters a day. This unexpected behavior defies what we know about cellular dynamics, and could be relevant to understand embryonic development or metastasis. Mechanical waves – such as seismic waves, sound, or waves in the sea – are a phenomenon easily explained by the laws of physics: when two particles collide, a wave travels through the surrounding material.

The study will take as a starting point the pioneering research conducted by IBEC’s Xavier Trepat on how cadherins interact in metastasis The pharmaceutical company Ferrer has created a consortium with the Institute for Bioengineering of Catalonia (IBEC) and the bioinformatics company Mind the Byte, located at the Barcelona Science Park (PCB), to study the development of new therapeutic molecules against cancer metastasis. The work will follow the research on cadherin interaction and its role in cells that cause metastasis conducted by Dr. Xavier Trepat, ICREA professor at IBEC and one of the few scientists to have won three grants from the European Research Council (ERC).

Ferrer, IBEC and Mind the Byte join forces to study new molecules against cancer metastasis

The study will take as a starting point the pioneering research conducted by IBEC’s Xavier Trepat on how cadherins interact in metastasis The pharmaceutical company Ferrer has created a consortium with the Institute for Bioengineering of Catalonia (IBEC) and the bioinformatics company Mind the Byte, located at the Barcelona Science Park (PCB), to study the development of new therapeutic molecules against cancer metastasis. The work will follow the research on cadherin interaction and its role in cells that cause metastasis conducted by Dr. Xavier Trepat, ICREA professor at IBEC and one of the few scientists to have won three grants from the European Research Council (ERC).

Xavier Trepat, ICREA professor and group leader at IBEC, was the guest star at the first anniversary celebration of Big Vang, La Vanguardia’s online science section At the event on 7th June, where Xavier shared the stage with the director of IRB Joan Guinovart, the relationship between scientists and journalists was discussed – a relationship that can sometimes be a little illusive, as journalist Cristina Saez put it, referring to the disagreements that can arise between the two sides when explaining science to the public. Along with fellow journalist Núria Jar, she introduced questions to the invited guests.

IBEC’s Xavier Trepat a guest star at Big Vang’s first anniversary

Xavier Trepat, ICREA professor and group leader at IBEC, was the guest star at the first anniversary celebration of Big Vang, La Vanguardia’s online science section At the event on 7th June, where Xavier shared the stage with the director of IRB Joan Guinovart, the relationship between scientists and journalists was discussed – a relationship that can sometimes be a little illusive, as journalist Cristina Saez put it, referring to the disagreements that can arise between the two sides when explaining science to the public. Along with fellow journalist Núria Jar, she introduced questions to the invited guests.

Researchers at IBEC and their collaborators at the Centre of Regenerative Medicine of Barcelona (CMR[B]) have developed a revolutionary new technique based on photoactivation (light activation), by which cells in deep tissue can activated and tracked in vivo without causing any damage. Manipulating protein expression to monitor cell behavior is a powerful tool in the field of biology.

Reaching new depths: a non-invasive solution for the activation of proteins in deep tissues

Researchers at IBEC and their collaborators at the Centre of Regenerative Medicine of Barcelona (CMR[B]) have developed a revolutionary new technique based on photoactivation (light activation), by which cells in deep tissue can activated and tracked in vivo without causing any damage. Manipulating protein expression to monitor cell behavior is a powerful tool in the field of biology.

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