Pere Roca-Cusachs, PI of the project, explains in this article the aim of the Mechano·Control project which is understanding the mechanical control of the biological function in order to abrogate breast tumour progression.
The consortium addresses this challenge thanks to an interdisciplinary research community with the aim of understanding cancer biomechanics from the single molecule to the whole organ scale. Ultimately, it’s hoped that the project will lead to the development of breast cancer treatments based on the new discoveries.
“Cells change their behaviour when they are in a stiff place; they further stiffen the tissue by secreting more matrix. If you convince the cells that they’re not in a stiff place, then they will stop secreting this, and this may help restore the normal stiffness of the tissue”
“What happens if we change the composition of the extra-cellular matrix to look more like cancer? What changes?” asks Roca-Cusachs. “We are developing mimics of this matrix, where we can dynamically change their properties. We can make the matrix get stiffer or softer by applying different kinds of light.”
You can read the article here:
We want to thank the EU Research Magazine for the article (EU Research WIN20/P17.)
The Mechano·Control project videos have been featured at the “Future Tech week” and at the European Research and Innovation Days event. After submitting the project videos to the “Spotlight Video Contest” of the Future Tech Week, boht videos have been selected to be aired in the session ‘Voices from the Future: EIC Pathfinder projects, stories, people, visions’ held online on the 22th September.
Future Tech Week provides EIC Pathfinder FET projects with a platform from which to blast their exciting findings, results and future paths to innovation to a wide range of stakeholders. It is a platform to showcase all the achievements in fields aligning with the European Commission’s priorities, including Artificial Intelligence and information technology, health and biotech, culture and society, energy and environment, and nanotech and materials. This year’s edition is taking place between 21st – 25th September. Future Tech Week features creative contributions from across Europe and beyond with a focus on Future and Emerging Technologies (FET).
The sessions entitled “Voices from the future: Pathfinder stories, people, visions”, organized in the frame of the Future Tech Week, will showcase EIC Pathfinder results from research to their exploitation into the market, through the valuable Keynote speech from Nobel Laureate Professor Edvard I. Moser (GRIDMAP), interview to the EIC Programme Manager Iordanis Arzimanoglou, the Keynote speech by Prof. Jerzy Langer – EIC Pilot Advisory Board member. Several roundtables will discuss about EIC Pathfinder future paths in a wide range of technological trends. The project videos selected by the “Spotlight video contest” will be streamed after Edvard I. Moser Keynote speech.
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.
Today, the European Molecular Biology Organization (EMBO) has released the names of the researchers who will join the prestigious organization, which has 88 Nobel laureates among its members. In total, 63 life science researchers have been recognized by the EMBO organization for their research career of excellence, among them, Pere Roca-Cusachs, principal investigator of the Institute of Bioengineering of Catalonia (IBEC) and associate professor at the Faculty of Medicine of the University of Barcelona (UB). Pere Roca-Cusachs’ pioneering research at IBEC is focused on the mechanobiology field.
Cutting-edge research in the physics of cancer
As leader of the “Cellular and Molecular Mechanobiology” group at IBEC, Prof. Roca-Cusachs focuses his research to unravel the mechanisms that cells and molecules use to detect and respond to mechanical forces and stimuli, such as, for example, tissue stiffness. These environmental stimuli determine how cells proliferate, differentiate, and move, and regulate processes such as embryonic development, tumour progression, or wound healing.
Since 2017, Pere Roca-Cusachs leads the “Mechano·Control” project, which, with funding from the European Union of more than 7 million euros, seeks to decipher and control how cells transmit and detect mechanical forces. The objective of Mechano·Control is to identify new tools to slow the progression of cancer and especially against breast cancer.
Among other recognitions, Pere Roca-Cusachs received the “Ciutat de Barcelona” award to life sciences 2018, for a study published in the Cell journal, where he identified a mechanism by which tissue rigidity regulates cell survival and proliferation, as well as its implications in diseases such as cancer and liver and lung fibrosis. In early 2019 he won the award of the “European Biophysical Societies Association (EBSA)” for his contributions in the field of mechanobiology. He is also a member of the “ICREA Academia” program of the Catalan Government.
“Being elected a member of EMBO is a great honour, due to the reputation of the organization and because it is a recognition that comes from my own scientific community. I hope to be worthy of this recognition, not only continuing with our research work, but also contributing to the dissemination and promotion of the importance of research on life sciences that EMBO represents throughout Europe”.
IBEC’s success at EMBO
The EMBO selects new scientists annually, candidate scientists must be nominated by current EMBO members and approved by another five members from different countries and then, they have to receive approval from the entire organization. In this edition, 63 candidacies from 25 different countries have been accepted, 52 of them have become part of the organization and 11 as associate members. Only three Spanish researchers are joining the organizaation and Pere Roca-Cusachs, who back in 2016 was already accepted in the “EMBO Young Investigator Programme”. The EMBO members are excellent scientists who carry out cutting-edge research in the different disciplines of the life sciences, among which there are 88 members who have received Nobel prizes. This new appointment is in addition to Xavier Trepat, also group leader at IBEC, who has been a member of EMBO since 2018.
EMBO is an organization of more than 1800 leading researchers that promotes excellence in the field of life sciences, both in Europe and worldwide. The organization’s primary goals are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a research environment where scientists can achieve their best work. Along with Pere Roca-Cusachs, researchers Maria Dolores Martin-Bermudo from the Pablo de Olavide University and Guillermina López-Bendito from the Institute of Neurosciences of San Juan de Alicante have also been chosen by the organization.
Xavier Trepat, group leader at IBEC and PI of the Mechano·Control consortium together with Raimon Sunyer, Senior researcher in Trepat’s lab, have written a Primer in Current Biology magazine on “Durotaxis”, a cell migration mechanism that might have a role in several disease states that include the stiffening of tissues.
Embryo development, tumour progression or the immune response against pathogens requires cell migration. Cells are not static, they move and are able to direct their migration, normally guided by spatial gradients in a physicochemical property of the cell microenvironment, such as chemical concentration for example, but it is also guided by the stiffness of their extra-cellular matrix (ECM).
Durotaxis was first reported in 2000 and is the tendency of single cells to follow stiffness gradients. Since it was first described, several studies have been carried out, mostly in vitro, as in vivo remains poorly studied. As technological advances bring new tools to probe ECM stiffness in living tissues, new roles for durotaxisin vivo are likely to emerge.
Durotaxis is normally positive, towards stiff regions, but it has also been observed as negative, from stiff to soft, some examples of this phenomenon are explained in this review.
In this piece, written by Xavier Trepat and Raimon Sunyer, they give an overview on the methods used to study durotaxis both in vitro and in vivo, and on the state of art of the mechanisms of durotaxis, which remains incompletely understood.
The researchers also explain that some cell types do not display significant durotaxis when migrating in isolation, but they durotax efficiently as cohesive clusters. Multicellular clusters can behave as a giant supracell, increasing its sensitivity to mechanical gradients. However, collective durotaxis has not yet been demonstrated in vivo but it is believed that this phenomenon could guide collective migration in pathological processes involving local changes in tissue stiffness. For instance, solid tumours are widely known to be stiffer than the surrounding tissue, which may favour or prevent collective invasion.
In conclusion, in this review the researchers state that durotaxis is emerging as a robust mechanism to drive directed migration of single cells and clusters. Key components include cell-ECM adhesion through molecular clutches and long-range force transmission across the cytoskeleton and cell-cell junctions. It is expected that durotaxis might be the cause of many migratory movements in vivo that are currently unexplained.
Read the full article here: Raimon Sunyer; Xavier Trepat, Durotaxis. Current Biol. 2020, 30, R383-R387
This past 2019 has been a great success concerning the outreach activities carried out within the Mechano·Control project. More than 320 people attended talks, workshops, discussions… related to mechanobiology.
Each year IBEC organises several workshops on mechanobiology where students explore how cells exert forces and they measure them and also create a cell membrane model. This year three schools with 25 students each have participated in this programme. Also, once a year 24 students that participate in a larger programme called “Crazy about bioengineering” come to Pere Roca-Cusachs and Trepat’s lab to do hands-on sessions on how cells perceive the surrounding environment, mechanobiology and biochemical responses.
London participated at the 2019 Pint of Science with a talk on how forces are
key to unveiling how life functions with an audience of more than 50 people
from different ages and backgrounds.
three presentations throughout the year addressed to patients and general
public about their research line on breast cancer, where more than 130 attended
Last but not least, INM also organised two experimental activities at their laboratories reaching 40 students and also mentoring lab practice to 5 secondary school students.
Pere Roca-Cusachs, coordinator of the Mechano·Control project and PI at the Institute for Bioengineering of Catalonia has been interviewed for the European Comission Digital Single Market news section.
Through the interview by Giordano Zambelli, Pere unfolds the aim of the project and it’s impact to society and also explains his experience working with FET.
Finding effective solutions to fight cancer is undoubtedly one of the main scientific challenges worldwide, whose success needs necessarily to build on innovative pathways of research. Mechano-Control aims to understand the physical forces that determine the spread of a wide range of diseases, with potentially vast impact on the development of new therapies.
The Mechano·Control project has launched a series of videos describing the aim of the project. In order to reach a broad audience and bring the reaserch closer to society and making it understandable, the first video explains through cartoons, the aim of the project and the research that is being carried out by the consortium members. The second video, shows the researchers behind the project. Mechano·Control is focused on the mechanical control of the biological function with the aim abrogate breast tumour progression.
More than 60 people attended the “Mechanobiology of Cancer Summer School 2019” organised by the Mechano·Control consortium. The summer school was held in Prullans, a tiny village located at the Catalan Pyrenees 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 morning sessions where dedicated to the keynote sessions from leading researchers in the mechanobiology field. The sessions left room to exchange opinions and doubts between the participants and the speakers. On the first day, Guillaume Salbreux (Francis Crick Institute) gave a lecture on “Physics of epithelial deformations” and Buzz Baum (Francis Crick Institute) on “Cancer cell division”. The second day started with Marija Plodinec’s (University Hospital Basel) keynote on “Nanomechanical profiling of living epithelial tissues in health and disease and potential applications in routine clinical setting” followed by Peter Friedl’s (St. Radboud University Nijmegen Medical Centre) intervention on Plasticity of adhesion and matrix guidance in cancer invasion and metastasis”. The last day started with Andrew Ewald (Johns Hopkins University School of Medicine for Cell Dynamics) and his talk on “Novel roles of cell adhesion in breast cancer metastasis” and to finish with the scientific sessions, Christina Scheel (St. Josef Hospital, Ruhr-University Bochum) with her lecture “Dynamic collagen deformation drives branching morphogenesis in mammary organoids derived from human breast tissue“.
The keynote sessions were followed by short talks from the attendees of the summer school, which created a space for sharing knowledge and exchanging the different research that is being carried out in different institutions around the world.
The afternoon sessions where more interactive and hands-on sessions with six different workshops organised by the Mechano·Control members. Marino Arroyo (Universitat Politècnica de Catalunya) gave an interactive workshop on “Vertex modelling in biomechanics” using the Matlab programme, Sergi Garcia-Manyes (King’s College London) on “Single molecule mechanics”, Manuel Gómez from Xavi Trepat’s lab (Institute for Bioengineering of Catalonia) on “Traction force microscopy”, Menno de Jong and Onno van den Boomen (Noviocell) on “Gel mechanics”, Patrick Derksen (University Medical Center Utrecht) on “Fundamentals of breast cancer biology” and Julieta Páez and Gulistan Kocer (Leibniz Institute for New Materials) on the “Chemistry of tuneable gels”.
Finally, the last day there was a poster session, where amongst the 30 posters, the keynote speakers had to give an award to the best poster. Adam Ouzeri, PhD at LaCaN – Cell and tissue mechanobiology, from Universitat Politècnica de Catalunya (UPC) won the prize for his poster “Upscaling active gel models of the actin cortex to epithelial mechanics”.
Not everything would be training, there was also time for leisure and social activities to promote networking between the participants, PI’s and keynote speakers. There was a hiking trip and a visit to the green house located near the hotel.
The ability to control key forces that drive biological functioning would be a boon for a number of medical fields. With a focus on breast cancer, an EU-funded project is bringing together different research communities to work towards understanding and controlling cellular mechanics.
Mechanical forces are created inside the body through the action of specific molecular bonds. Being able to control these would enable a giant leap forward in fields such as oncology, regenerative medicine and biomaterial design.
Tapping the potential of cellular mechanics requires the development and integration of a number of disparate technologies. The EU-funded MECHANO-CONTROL project is addressing this challenge, assembling an interdisciplinary team to design and carry out pertinent research. The scientists involved are specifically targeting new ways to impair or abrogate breast tumour progression.
The project’s ultimate aim is to understand and learn to control the full range of cellular mechanics. To do so, scientists need to find new ways to measure and manipulate complex cellular processes – from the nanometre to the metre scale.
At all stages, the MECHANO-CONTROL team is integrating experimental data with multi-scale computational modelling. With this approach, the aim is to develop specific therapeutic approaches beyond the current paradigm in breast cancer treatment.
Going further, the general principles delineated by MECHANO-CONTROL could also have high applicability in other areas of oncology, as well as regenerative medicine and biomaterials. This has the potential to bring new treatments and relief from suffering for many.
Taking it scale by scale
Working at the nanometric, molecular level, MECHANO-CONTROL researchers are developing cellular microenvironments, enabled by substances that mimic naturally occurring cell components.
On the cell-to-organ scale, the team is combining controlled microenvironments and interfering strategies with the development of techniques to measure and control mechanical forces and adhesion in cells and tissues, and to evaluate their biological response.
At the organism scale, researchers are establishing how cellular mechanics can be controlled.
A research team led by the IBEC, in collaboration with the CMR [B], discovers a mechanism that generates binucleated cells.This mechanism has been identified during the regeneration of the heart of the zebrafish, and could be associated with the extraordinary regenerative power of this animal.
After an acute heart lesion, such as a myocardial infarction, the human heart is unable to regenerate. The adult cardiac cells cannot grow and divide to replace the damaged ones, and the lesion becomes irreversible. But this does not happen in all animals. A freshwater fish native to Southeast Asia, known as a zebrafish, can completely regenerate its heart even after 20% ventricular amputation.
This extraordinary regenerative capacity has attracted the attention of
researchers from all over the world, who see the range of possibilities that
would be opened up if this mechanism of cell regeneration could be applied in
In an article
published today in the Nature Materials journal, a team of researchers from the
Institute of Bioengineering of Catalonia (IBEC) led by Xavier Trepat, in
collaboration with the Centre for Regenerative Medicine in Barcelona (CMR [B]),
have discovered a surprising mechanism by which zebrafish heart cells move and
divide during regeneration.
focused on the epicardium, which is the layer of cells on the outer surface of
the heart. Although the epicardium cells represent only a small fraction
of the heart’s mass, they play a fundamental role in its regeneration. “The
epicardium is the origin of several of the heart’s cell types, and secretes
biochemical signals that tell the cells what they have to do at all times. It’s
a kind of regeneration ‘hub’”, states Angel Raya, ICREA Researcher and
director of CMRB.
After a heart
lesion, the epicardium cells begin to divide and move en masse to cover the
wound. Researchers have observed that, during this process, the cells become
binucleated: they duplicate the genetic material and separate it into two
nuclei, but they are not divided into two independent cells. “We were very
surprised to discover cells that, instead of having one nucleus, as is the case
in most tissues, they have two nuclei, and each of them contains a copy of the
cell’s DNA” says Trepat, ICREA researcher at IBEC and associate professor of
the University of Barcelona.
discovered that the mechanism by which cells become binucleated has a
biomechanical origin. Once DNA has already separated into two nuclei, most
animal cells form a contractile ring at its centre. As it contracts, this ring
divides the mother cell into two daughter cells. In the case of the heart cells
of the zebrafish, the study shows that the ring adheres to the fibres of its
environment so that it cannot tighten. The result is that the two daughter
cells cannot separate despite having correctly duplicated their DNA.
is a well-known phenomenon in cancer, because it is a cause of genetic
instability. In other words, cancer cells lose control of the proteins they
synthesise and behave pathologically. In the case of the heart of zebrafish,
the multinucleation is physiological and does not seem to cause any problem”,
states Marina Uroz, the article’s main author. The next step will be to study
the role of multinucleated cells during the regeneration of the heart and other
Dr. Trepat and Dr. Raya are part of CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine)