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 tweezers, Atomic Force Microscopy, traction microscopy, and microfabricated force sensors with molecular biology, advanced optical microscopy, and theoretical modelling.
Sensing rigidity: Using this multi-disciplinary approach, we have recently 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. Recently, we have begun to explore how force transmission to the nucleus affects the dynamics of transcriptional regulators, such as YAP (Elosegui-Artoal et al., 2017, Cell).
Sensing the environment: We are currently 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 recently 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).
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
Alberto Elosegui Artola | Postdoctoral Researcher
Laura Faure | Postdoctoral Researcher
Zanetta Zoi (Jenny) Kechagia | Postdoctoral Researcher
Anabel-Lise Le Roux | Postdoctoral Researcher
Ignacio Viciano Gonzalo | Postdoctoral Researcher
Ignasi Granero Moya | PhD Student
Marc Molina Jordán | PhD Student
Marina Pavlova | PhD Student
Xarxa Quiroga Álvarez | PhD Student
Srivatsava Viswanadha Venkata Naga Sai | PhD Student
Susana Usieto Camín | Laboratory Technician
Diego Baranda Martínez-Abascal | Masters Student
Aurora Dols Pérez | Visiting Researcher
|MECHANOCONTROL · Mechanical control of biological function (2017-2021)||European Commission, FET Proactive||Pere Roca-Cusachs|
|TALVIN · Inhibiting mechanotransduction for the treatment of pancreatic cancer (2018-2020)||European Commission, FET Innovation Launchpad||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|
|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|
|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|
|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
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.
Nuria Montserrat and Pere Roca-Cusachs interviewed in the article “10 scientific advances that will revolutionize the future” of the newspaper Ara, talking about 3D tissue printing and mechanobiology.
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.
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.