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.
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. 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. 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
Ion Andreu Arzuaga | Postdoctoral Researcher
Amy Beedle | Postdoctoral Researcher
Laura Faure | Postdoctoral Researcher
Kenta Homma | Postdoctoral Researcher
Zanetta Zoi (Jenny) Kechagia | Postdoctoral Researcher
Anabel-Lise Le Roux | Postdoctoral Researcher
Ignacio Viciano Gonzalo | Postdoctoral Researcher
Miguel González Martín | PhD Student
Ignasi Granero Moya | PhD Student
Marc Molina Jordán | PhD Student
Srivatsava Viswanadha Venkata Naga Sai | PhD Student
Susana Usieto Camín | Laboratory Technician
Ona Baguer Colomer | Masters Student
Mario Díez Hermoso | Masters Student
Gavin McQuarrie | Masters Student
|MECHANOCONTROL · Mechanical control of biological function (2017-2022)||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|
|MECNUC · Estudio del control mecánico de la localización nuclear de proteínas (2020-2023)||MINECO
Retos investigación: Proyectos I+D
|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|
|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
Researchers led by Pere Roca-Cusachs appear in different media for their study published in the prestigious journal “Nature Communications” that discovers how force dynamics affect cells, and living tissues.
Researchers, led by Pere Roca-Cusachs at the Institute for Bioengineering of Catalonia (IBEC) discover how force dynamics affect cells, and living tissues. The results give an insight into the critical mechanical processes that occur in different diseases such as cancer.
Roger Oria wins the XXIV Doctors’ Senate Award of the University of Barcelona (UB) for his thesis on mechanobiology, an emerging discipline that can help identify new tools to stop pathologies associated with tissue stiffness, such as cancer.
Xavier Trepat and Pere Roca-Cusachs, group leaders at IBEC, appear on the journal “ABC” explaining their research project that they will carry out thanks to funding from “la Caixa” as part of the «Health Research Call ».
IBEC researchers Elena Martínez, Xavier Trepat and Pere Roca-Cusachs aim to understand the processes that promote metastasis in colorectal cancer using innovative bioengineering tools, such as bioprinting and microscopy capable of revealing forces at the cellular level.
The results will be translated into a device that will recreate the tumor environment from cancer cells derived from patients, as well as a new technology that will allow to visualize how physical forces affect the nuclei of metastatic cells.
Pere Roca-Cusachs, group leader at the Institute for Bioengineering of Catalonia (IBEC) and associate professor at the Faculty of Medicine of the University of Barcelona (UB), has been chosen to join the European Molecular Biology Organization (EMBO) , a prestigious network that brings together some of the most brilliant researchers in the world.
Roca-Cusachs is a pioneer in Europe in the mechanobiology field and in the study of how physical forces affect diseases such as cancer.
Pere Roca-Cusachs, principal investigator at IBEC, is the only Catalan chosen this year to join the prestigious European Molecular Biology Organization (EMBO).
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.