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Cellular and molecular mechanobiology

About

Every time we blink, move a hand, draw a breath, or walk, cells in our body exert, transmit, withstand, and detect forces. This mechanical interaction with the environment determines how cells proliferate, differentiate, and move, and regulates development, tumorigenesis or wound healing.

Our research aims precisely at unraveling the mechanisms that these molecules use to detect and respond to mechanical stimuli like forces or tissue rigidity, triggering downstream cell responses.

Just like biochemical stimuli initiate signaling cascades, mechanical forces affect the links and conformation of a network of molecules connecting cells to the extracellular matrix.

To this end, we combine biophysical techniques like magnetic and optical tweezers, Atomic Force Microscopy, traction microscopy, and microfabricated force sensors with molecular biology, advanced optical microscopy, and theoretical modelling.

Sensing the environment: Using this multi-disciplinary approach, we have unveiled a molecular mechanism that cells employ to detect and respond to the rigidity of their environment, which could be crucial in breast tissue and breast cancer (Elosegui-Artola et al., 2016 Nat. Cell Biol., and Elosegui-Artola et al. 2014, Nature Mater.). This mechanism is mediated by what is known as a “molecular clutch”: in a surprising analogy with a car engine, cells can be understood as a molecular network that can engage and disengage from its environment, just as the clutch of a car. This affects force transmission from the environment to cells, and also within different cell components. We are also expanding on the idea of the molecular clutch, to explore how cell molecular engines sense not only mechanical rigidity, but other important parameters from their environment: for instance, the composition and distribution of ligands in the extracellular matrix, or other cells. In this regard, we uncovered that this concept can explain how cells sense the spatial distribution of ligands in the extracellular matrix (Oria et al., Nature 2017). We have also demonstrated that cell-cell force transmission, mediated by a molecular clutch, is essential for cells to sense gradients in stiffness (Sunyer et al., Science 2016, in collaboration with the group of Xavier Trepat).

Nuclear mechanotransduction: Forces applied to cells are transmitted all the way to the cell nucleus, where they affect its function. We are studying how this force transmission affects the dynamics of transcriptional regulators, such as YAP (Elosegui-Artola et al., 2017, Cell), and how this affects cell function.

The membrane as a mechanosensor: Due to its mechanical properties, the plasma membrane itself can respond to forces and act as a mechanosensor. Recently, we have shown that cell membranes can use purely physical principles to adapt their shape in response to mechanical forces (Kosmalska et al., 2015, Nat. Commun.). We are currently studying how cells harness this physical membrane behavior to respond to signals from their environment.

Ultimately, when we determine the molecular mechanisms that communicate cells with their environment, we will understand how forces determine development when things go right, and tumor formation when they go wrong.

Video: How tissue stiffness activates cancer

 

Staff

Projects

NATIONAL PROJECTSFINANCERPI
MECNUC · Estudio del control mecánico de la localización nuclear de proteínas (2020-2023)MINECO
Retos investigación: Proyectos I+D
Pere Roca-Cusachs
BLOCMEC Development of small molecules to block mechanotransduction for pancreatic cancer therapy (2021-2023)MICIU, Proyectos Pruebas de ConceptoPere Roca-Cusachs
INTROPY INhibiting mechanoTRansduction for Oncology theraPY (2021-2023)ACCIO, Tecniospring IndustryMamatha Nijaguna
INTERNATIONAL PROJECTSFINANCERPI
MECHANOCONTROL · Mechanical control of biological function (2017-2021)European Commission, FET ProactivePere Roca-Cusachs
TALVIN · Inhibiting mechanotransduction for the treatment of pancreatic cancer (2018-2021)European Commission, FET Innovation LaunchpadPere Roca-Cusachs
MECHANOSITY Mechanical regulation of cellular behaviour in 3D viscoelastic materials (2019-2022)European Commission, MARIE CURIEAlberto Elosegui
PRIVATELY-FUNDED PROJECTSFINANCERPI
Mech4Cancer · Enabling technologies to map nuclear mechanosensing: from organoids to tumors (2020-2023)Obra Social La Caixa
Health Research Call
Pere Roca-Cusachs
Understanding YAP-mediated mechanotransduction in pancreatic cancer (2020-2023)Fundació La Marató de TV3Pere Roca-Cusachs
Understanding and measuring mechanical tumor properties to improve cancer diagnosis, treatment, and survival: Application to liquid biòpsies (2017-2022)Obra Social La Caixa Pere Roca-Cusachs
FINISHED PROJECTSFINANCERPI
Desarrollo de una terapia innovadora para el tratamiento de los tumores sólidos mediante la inhibición de la mecanotransducción (2018-2020)MINECO, Subprograma Retos-ColaboraciónPere Roca-Cusachs
Understanding and measuring mechanical tumor properties to improve cancer diagnosis, treatment, and survival: Application to liquid biopsies (2017-2020)Obra Social La CaixaPere Roca-Cusachs
IMREG El sistema acoplado entre integrinas y proteínas adaptadoras como regulador mecánico del comportamiento celular (2016-2020)MINECO, Proyectos I+D ExcelenciaPere Roca-Cusachs
MECHANOMEMBRANE Redes mecanoquímicas en la membrana plasmática (2017-2018)MINECO, Subprograma Estatal de Generación de Conocimiento “EUROPA EXCELENCIA”Pere Roca-Cusachs
Stromal stiffness in tumor progression (2014-2017)Fundació La Marató de TV3Pere Roca-Cusachs
MECBIO Red de Excelencia en Mecanobiología (2014-2016)MINECO, Subprograma Estatal de Generación de Conocimiento “REDES DE EXCELENCIA”Pere Roca-Cusachs
Inhibiting mechanostransduction as a novel therapy in the treatment of solid tumors (2017-2018)Obra Social La CaixaPere Roca-Cusachs

Publications

Click here for a list of publications by Pere Roca-Cusachs with IBEC affiliation.

Click here for a full list of publications including those affiliated to other organisations.

Equipment

  • Confocal Microcopy
  • Traction Microscopy
  • Live cell fluorescence microscopy
  • Cell stretching
  • Cell culture
  • Magnetic Tweezers
  • Atomic Force Microscopy
  • Surface Micro/Nano-patterning
  • Optical tweezers

Collaborations

  • Dr. Nils Gauthier
    Mechanobiology Institute, Singapore
  • Prof. Miguel Ángel del Pozo
    Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid
  • Prof. Marino Arroyo
    UPC, Barcelona
  • Prof. Ada Cavalcanti
    University of Heidelberg, Germany
  • Satyajit Mayor
    National Centre for Biological Sciences, Bangalore, India
  • Sergi Garcia-Manyes
    King’s College, London, UK
  • Cheng Zhu
    Georgia Tech, Atlanta, USA
  • Louise Jones
    Barts Cancer Institute, London, UK
  • Aránzazu del Campo
    INM Saarbrücken, Germany
  • Johan de Rooij and Patrick Derksen
    UMC Utrecht, the Netherlands 
  • Johanna Ivaska
    University of Turku, Finland 
  • Jacco van Rheenen
    Netherlands Cancer Institute, Netherlands 
  • Isaac Almendros and Ramon Farré
    UB, Barcelona
  • Marc Martí-Renom
    CNAG, Barcelona
     

Clinical collaborations

  • University Medical Centre Utrecht 
  • Vall d’hebron Institute of Oncology 

News

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.

IBEC recieves funding for three projects thanks to la Marató 2018

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.

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.

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.

Pere Roca-Cusachs, group leader at IBEC and assistant professor at the University of Barcelona, has won the 2019 Young Investigator Prize for his contributions to the field of mechanobiology. The award is given by the European Biophysical Societies Association (EBSA). EBSA association grants this prize every two years. The last winner of the prize was Philipp Kukura from the University of Oxford in the UK in 2017. The prize recognises an investigator who has defended his thesis 12 years ago or less across Europe and awards him with 2000€ and a medal as well as be expected to contribute an article to the European Biophysics Journal.

Pere Roca winner of EBSA Young Investigator’s Prize

Pere Roca-Cusachs, group leader at IBEC and assistant professor at the University of Barcelona, has won the 2019 Young Investigator Prize for his contributions to the field of mechanobiology. The award is given by the European Biophysical Societies Association (EBSA). EBSA association grants this prize every two years. The last winner of the prize was Philipp Kukura from the University of Oxford in the UK in 2017. The prize recognises an investigator who has defended his thesis 12 years ago or less across Europe and awards him with 2000€ and a medal as well as be expected to contribute an article to the European Biophysics Journal.

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.

Mechanobiology of Cancer Summer School 2019

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.

The biotechnology company Iproteos, IBEC and the Vall d’Hebron Research Institute (VHIR) are set to develop an innovative treatment to slow down, stop and even reverse the growth of solid tumors, which represent more than 90% of cancer cases. It’s a family of peptidomimetic drugs based on a totally new anti-tumor action mechanism, the result of several years of research by Pere Roca-Cusachs’ group at IBEC. The Translational Research Group on Cancer in Children and Teenagers at VHIR will evaluate candidate drugs, developed with Iproteos’ IPROTech technology, in pediatric tumours in vitro and in vivo.

Iproteos, IBEC and VHIR to develop an innovative therapy against solid tumors

The biotechnology company Iproteos, IBEC and the Vall d’Hebron Research Institute (VHIR) are set to develop an innovative treatment to slow down, stop and even reverse the growth of solid tumors, which represent more than 90% of cancer cases. It’s a family of peptidomimetic drugs based on a totally new anti-tumor action mechanism, the result of several years of research by Pere Roca-Cusachs’ group at IBEC. The Translational Research Group on Cancer in Children and Teenagers at VHIR will evaluate candidate drugs, developed with Iproteos’ IPROTech technology, in pediatric tumours in vitro and in vivo.

Researchers at IBEC have discovered that cell division in epithelial tissues is regulated by mechanical forces. This revelation could potentially open avenues to a greater understanding of the uncontrolled proliferation of cancer cells in tumors, and their possible regulation by means of physical forces. Publishing in the June edition of Nature Cell Biology, the research group of ICREA professor Xavier Trepat, group leader at IBEC and associate professor at the University of Barcelona (UB), describe how the mechanical state of epithelial tissues – the continuous sheets of cells that cover all the exposed surfaces of the body – is related to the cell cycle and cell division.

Physical forces regulate cell division

Researchers at IBEC have discovered that cell division in epithelial tissues is regulated by mechanical forces. This revelation could potentially open avenues to a greater understanding of the uncontrolled proliferation of cancer cells in tumors, and their possible regulation by means of physical forces. Publishing in the June edition of Nature Cell Biology, the research group of ICREA professor Xavier Trepat, group leader at IBEC and associate professor at the University of Barcelona (UB), describe how the mechanical state of epithelial tissues – the continuous sheets of cells that cover all the exposed surfaces of the body – is related to the cell cycle and cell division.

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.

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