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
Laura Faure | Postdoctoral Researcher
Zanetta Zoi (Jenny) Kechagia | Postdoctoral Researcher
Anabel-Lise Le Roux | Postdoctoral Researcher
Víctor González Tarragó | PhD Student
Ignasi Granero Moya | PhD Student
Xarxa Quiroga Álvarez | PhD Student
Srivatsava Viswanadha Venkata Naga Sai | PhD Student
Marc Molina Jordán | Research Assistant
Marina Pavlova | Research Assistant
Oriol Mañé Benach | Laboratory Assistant
Last week IBEC’s PhD students headed off to Mas Colltort in Sant Feliu de Pallarols for the first ever IBEC PhD retreat.
IBEC group leader Pere Roca-Cusachs is the Journal of Cell Science’s ‘cell scientist to watch’ in its current edition.
An IBEC project pitch won third prize in a Technology Transfer Competition at last week’s Onco Emergence Forum.
Researchers at IBEC have discovered that cell division in epithelial tissues is regulated by mechanical forces.
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.
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.
The Executive Council of the Sociedad de Biofísica de España has awarded the 2018 Enrique Pérez-Payá SBE-40 prize to Pere Roca-Cusachs, IBEC group leader and associate professor at the UB, for his outstanding contributions to uncovering the physical basis of cellular responses to mechanical signals.
On Friday the IBEC-managed Spanish Nanotechnology Platform, NanoMed Spain, co-hosted the fifth edition of Nano World Cancer Day, a global initiative organized as part of World Cancer Day.
Pere Roca-Cusachs, group leader at IBEC and assistant professor at the University of Barcelona, has won the 2017 City of Barcelona Award for the life sciences.
The way cells find their way around is by ‘groping’ rather than seeing their surroundings: this is the main conclusion of a study published in Nature last week involving several IBEC groups and their collaborators.
In their effort to shed light on the role that physical forces play in the body, Pere Roca-Cusachs’ group at IBEC has shown how these forces ‘switch on’ the expression of genes that may result in cancer.
Three IBEC group leaders – Pere Roca-Cusachs, Vito Conte and Xavier Trepat – consolidate the institute’s leadership in mechanobiology by publishing a review of the field in Nature Cell Biology.
On Friday last week MECHANOCONTROL, the largest European project ever coordinated at IBEC, held its kick-off meeting at the institute.
In a study published today in Nature Cell Biology and supported by Obra Social “la Caixa”, researchers at IBEC have identified an interaction between two proteins that enables cancerous cells to use the physical forces of healthy cells to start tumor metastasis.
January 2017 sees the start of the largest European project ever coordinated at IBEC, Pere Roca-Cusachs’ MECHANOCONTROL, which aims to come up with new therapeutic or diagnostic approaches for cancer and other diseases.
Two IBEC projects have been granted funding as part of the 2016 CaixaImpulse programme, which is organized by the ”la Caixa” Foundation and Caixa Capital Risc.
IBEC junior group leader and UB assistant professor Pere Roca-Cusachs has been accepted into the prestigious EMBO Young Investigator Programme.
IBEC junior group leader and UB assistant professor Pere Roca-Cusachs is one of ten finalists selected for the American Society for Cell Biology’s Gibco Emerging Leader Prize.
A new phenomenon, collective durotaxis, opens new avenues to control tumor growth and improve wound healing.
Junior group leader Pere-Roca Cusachs took part in the second Pint of Science event, a science festival that takes place simultaneously in a dozen countries all over the world.
Researchers at IBEC have revealed how tissue rigidity activates cancer, new knowledge that could potentially lead to new strategies to impair or even halt the growth of tumours.
In a paper published in Nature Cell Biology, IBEC junior group leader Pere Roca Cusachs and his collaborators at Columbia University and Singapore’s Mechanobiology Institute reveal the potential of a protein found in cell cytoskeletons as a repressor of cancer.
A study by the Institute for Bioengineering of Catalonia (IBEC) reveals how cells withstand breakage during the constant changes in shape and volume experienced in most biological processes.
At a press conference at the Obra Social “la Caixa”’s Palau Macaya earlier today, Xavier Trepat, group leader at the Institute for Bioengineering of Catalonia (IBEC), Enric Banda, director of the department of Science and Environment of the Obra Social ”la Caixa”, and Josep Samitier, director of IBEC, described a study published in Nature Cell Biology which sheds new light on how to control metastasis.
The cover of Nature Materials featuring the Cellular and Respiratory Biomechanics group’s recent paper on how mammary cells detect tissue stiffening is out now.
Alberto Elosegui and Pere Roca-Cusachs’ Nature Materials paper gets lots of press coverage in newspapers, TV and radio today. In the study, they describe for the first time how mammary cells detect tissue stiffening, which is key to the development of breast cancer.
A study by IBEC researchers reveals in Nature Materials how mammary cells detect tissue stiffening, which is key to the development of breast cancer.
Junior group leader Pere Roca-Cusachs has received funding from 2012’s La Marató de TV3 for his project “Stromal stiffness in Tumor Progression”.
The October cover of Current Opinion in Cell Biology (the reference opinion journal in cell biology, with impact factor 12) features research by IBEC’s Pere Roca and Xavier Trepat, who together with Raimon Sunyer from the UB have published a review paper in the issue, “Mechanical guidance of cell migration: lessons from chemotaxis”.
An IBEC researcher and his collaborators uncover the crucial role of two molecules in enabling cells to communicate with their environment.
|MECHANOCONTROL Mechanical control of biological function (2017-2021)||European Commission, FET Proactive||Pere Roca-Cusachs|
|MECHANOMEMBRANE Redes mecanoquímicas en la membrana plasmática (2017-2018)||MINECO, Subprograma Estatal de Generación de Conocimiento “EUROPA EXCELENCIA”||Pere Roca-Cusachs|
|IMREG El sistema acoplado entre integrinas y proteínas adaptadoras como regulador mecánico del comportamiento celular (2016-2019)||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|
|Inhibiting mechanostransduction as a novel therapy in the treatment of solid tumors (2017-2018)||Obra Social La Caixa||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|
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