Primer on “Durotaxis”

Molecular clutch model proposed to explain durotaxis.
Molecular clutch model proposed to explain durotaxis (Current Biology)

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 durotaxis in 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

Great success of the 2019 Mechano·Control outreach activities

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.

King’s College 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.

UMCU organised three presentations throughout the year addressed to patients and general public about their research line on breast cancer, where more than 130 attended the meetings.

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.

PROJECTS STORY: The study of mechanical forces opens a promising front in the fight against cancer

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.

Read the full interview here: The study of mechanical forces opens a promising front in the fight against cancer

Mechano·Control project made easy

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.

Great success of the Mechanobiology of Cancer Summer School 2019 organised by the Mechano·Control project

Opening of the Mechanobiology of Cancer Summer School 2019

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.


Christina Scheel during her keynote presentation

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.


Marino Arroyo during his workshop

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”.

Poster session

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”.



“Wet lab scientists get wet outside the bench” Group photo

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.

Research to help battle breast cancer

Picture Partners #30814684, source: stock.adobe.com 2019

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.

Original piece of news: European Comission Research to help battle breast cancer

Binucleated cells could be the key in heart regeneration

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.

Cells of the epicardium of the zebrafish with two nuclei (in blue)

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 human therapies.

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.

Researchers have 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.

Researchers have 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.

“Multinucleation 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 organs.

Dr. Trepat and Dr. Raya are part of CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine)

Pere Roca-Cusachs and Antoine Khalil participate at the 2019 Gordon Research Conference

Pere Roca-Cusachs and Antoina Khalil in Lucca during the GRC

Last 5th-10th May was held the 2019 Gordon Research Conference on “Fibronectin, Integrins and Related Molecules” where Pere Roca-Cusachs from IBEC and Antoine Khalil from UMCU presented talks discussing Mechanocontrol results on how mechanical signals and the extracellular matrix regulate cell responses and tumour invasion. During the keynote session titled “Mechanisms and Mechanics of Integrin ECM Connections” Pere Roca-Cusachs gave a talk on “Exploring the Substrate Dependence of Integrin-Mediated Mechanotransduction”. Antoine gave an oral presentation where he described how cell-ECM adhesion regulates the positioning of basal cells and their specification into invasive leader cells during collective invasion of breast cancer organoids.

The Gordon Research Conference was held in Lucca, Italy and is the premier international conference for academic, government and industry scientists interested in understanding how integrins and the extracellular matrix regulate virtually every aspect of cell and tissue function. The program of the conference reflected the interdisciplinary nature of the integrin and extracellular matrix field, spanning different areas of biology from inflammation to mechanobiology, cell migration, stem cells, development, and cancer. During the meeting unpublished data was highlighted and stimulated active discussion among all participants.

Registration for Mechanobiology of Cancer Summer School 2019 is now opened

The MECHANO·CONTROL consortuium is launching the website for the “Mechanobiology of Cancer Summer School 2019” for the application process and registration.

The application period opens today until the 8th May 2019, where you can submint an abstract if you are interested in giving a short talk during the summer school.

The application does not guarantee acceptance to the Summer School due to the limited number of participants, an email with the resolution of the applicaton process will be sent on June 15th 2019.

The summer school will be held in La Cerdanya at the Eco-Resort located in Prullans in the Catalan Pyrenees.

The participation fee is 300€ (taxes not included) and includes accomodation in shared double room (from 17th-20th September 2019), full-board, workshops and conferences, leisure activities and shuttle bus from Barcelona to the venue.

Two more exchanges within the Mechano·Control consortium

IBEC is hosting two members from the Mechano·Control network. On the one hand, Dimitri Kaurin, PhD student from Marino Arroyo group at Universitat Politècnica de Catalunya (UPC) that will be staying at IBEC for at least one year and on the other hand, Amy Beedle, postdoc from Sergi Garcia-Manyes at Kings College London (KCL).

Dimitri Kaurin started his stay at Pere Roca-Cusachs’ laboratory in December 2018 and it is planned to be for at least a year. One of the objectives of Dimitri’s stay is to work on a protocol to study cell-cell adhesion using a controlled system based on lipid bilayers of controlled viscosity. “Using AFM technique, we expect to access some information about cell-cell adhesion under force” says Dimitri. In the context of this research he will also visit Manuel Salmeron laboratory in Glasgow University this march to learn some techniques about functionalizing lipid bilayers with cadherins.


Dimitri Kaurin working in the laboratory at IBEC

On the other hand, Amy Beedle arrived this past January to Pere Roca-Cusachs’ laboratory. In the Garcia-Manyes lab Amy was looking at how mechanical forces can trigger conformational changes in individual proteins. Here at IBEC, she wants to incorporate the results at the single molecule level with the cellular level, to try to understand how individual bonds and proteins can contribute to cellular mechanosensing. “My aim is to expand my expertise in single molecule force spectroscopy to a larger cellular context” adds Amy.

Amy Beedle working in the laboratory at IBEC

This is the first time that both UPC and KCL teams meet with IBEC to share skills and ideas within the project’s framework.