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
Pere Roca-Cusachs Soulere
|MECNUC · Estudio del control mecánico de la localización nuclear de proteínas (2020-2023)||MINECO|
Retos investigación: Proyectos I+D
|BLOCMEC Development of small molecules to block mechanotransduction for pancreatic cancer therapy (2021-2023)||MICIU, Proyectos Pruebas de Concepto||Pere Roca-Cusachs|
|INTROPY INhibiting mechanoTRansduction for Oncology theraPY (2021-2023)||ACCIO, Tecniospring Industry||Mamatha Nijaguna|
|MECHANOCONTROL · Mechanical control of biological function (2017-2021)||European Commission, FET Proactive||Pere Roca-Cusachs|
|TALVIN · Inhibiting mechanotransduction for the treatment of pancreatic cancer (2018-2021)||European Commission, FET Innovation Launchpad||Pere Roca-Cusachs|
|MECHANOSITY Mechanical regulation of cellular behaviour in 3D viscoelastic materials (2019-2022)||European Commission, MARIE CURIE||Alberto Elosegui|
|Mech4Cancer · Enabling technologies to map nuclear mechanosensing: from organoids to tumors (2020-2023)||Obra Social La Caixa|
Health Research Call
|Understanding YAP-mediated mechanotransduction in pancreatic cancer (2020-2023)||Fundació La Marató de TV3||Pere 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|
|Desarrollo de una terapia innovadora para el tratamiento de los tumores sólidos mediante la inhibición de la mecanotransducción (2018-2020)||MINECO, Subprograma Retos-Colaboración||Pere Roca-Cusachs|
|Understanding and measuring mechanical tumor properties to improve cancer diagnosis, treatment, and survival: Application to liquid biopsies (2017-2020)||Obra Social La Caixa||Pere Roca-Cusachs|
|IMREG El sistema acoplado entre integrinas y proteínas adaptadoras como regulador mecánico del comportamiento celular (2016-2020)||MINECO, Proyectos I+D Excelencia||Pere 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 TV3||Pere 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 Caixa||Pere Roca-Cusachs|
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.
- Confocal Microcopy
- Traction Microscopy
- Live cell fluorescence microscopy
- Cell stretching
- Cell culture
- Magnetic Tweezers
- Atomic Force Microscopy
- Surface Micro/Nano-patterning
- Optical tweezers
- Dr. Nils Gauthier
Mechanobiology Institute, Singapore
- Prof. Miguel Ángel del Pozo
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid
- Prof. Marino Arroyo
- 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
- Marc Martí-Renom
- University Medical Centre Utrecht
- Vall d’hebron Institute of Oncology
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.
IBEC group leader Pere Roca-Cusachs is the Journal of Cell Science’s ‘cell scientist to watch’ in its current edition.
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 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.