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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

IBEC group leaders Pere Roca-Cusachs and Elena Martinez featured in an article in Ara magazine at the weekend that discussed how understanding mechanical forces and their effect on cellular processes can open new avenues in the diagnosis and treatment of diseases such as cancer.

“Les lleis de Newton prometen una nova revolució mèdica”

IBEC group leaders Pere Roca-Cusachs and Elena Martinez featured in an article in Ara magazine at the weekend that discussed how understanding mechanical forces and their effect on cellular processes can open new avenues in the diagnosis and treatment of diseases such as cancer.

IBEC junior group leader and UB assistant professor Pere Roca-Cusachs has been accepted into the prestigious EMBO Young Investigator Programme. EMBO, the European Molecular Biology Organization, chooses some of the best young group leaders in Europe through a highly competitive annual selection. Pere presented his research plan for the next five years to an international panel in Heidelberg at the beginning of October. “I’m really delighted to have been accepted,” says Pere, who is the first ever IBEC researcher to be selected for the programme, and the only one from Spain this year.

IBEC’s first EMBO Young Investigator

IBEC junior group leader and UB assistant professor Pere Roca-Cusachs has been accepted into the prestigious EMBO Young Investigator Programme. EMBO, the European Molecular Biology Organization, chooses some of the best young group leaders in Europe through a highly competitive annual selection. Pere presented his research plan for the next five years to an international panel in Heidelberg at the beginning of October. “I’m really delighted to have been accepted,” says Pere, who is the first ever IBEC researcher to be selected for the programme, and the only one from Spain this year.

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