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.


Pere Roca winner of EBSA Young Investigator’s Prize

Pere Roca-Cusachs

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 across Europe who has defended his thesis 12 years ago or less and awards him with 2000€ and a medal as well as be expected to contribute an article to the European Biophysics Journal. The decision of the winning researcher is made by the Executive Committee based on scientific excellence, leadership and creativity.

The award ceremony will take place in Madrid during the 12th EBSA 10th ICBP-IUPAP European Biophysics Congress from 20-24 of July. During the congress, Pere will be giving a lecture and receive his Young Investigator’s Prize.

The European Biophysical Societies Association was formed in 1984 as a non-profit making organisation, with the objectives “to advance and disseminate knowledge of the principles, recent developments and applications of biophysics, and to foster the exchange of scientific information among European biophysicists and biophysicists in general”. It is composed of the Biophysical Societies in the European area and is managed by an Executive Committee. EBSA is associated with the international organizations International Union for Pure and Applied Biophysics (IUPAB) and Initiative for Science in Europe (ISE) and owns the European Biophysics Journal.

Mechanobiology of Cancer Summer School 2019

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.

Attendance to the Summer School is open to all students, post-docs, and professionals interested, although priority will be given to junior scientists (up to post-doctoral stage).

Soon, we will be launching the Mechanobiology of Cancer Summer School 2019 website, where you will find more information about the activities that will be held during the summer school, information on how to register, and the deadlines both for the registration and abstract submission.

The 6 confirmed speakers who will attend the summer school are:

  • Marija Plodinec (University Hospital Basel)
  • Andrew Ewald (Johns Hopkins University School of Medicine)
  • Peter Friedl (Radboud University Nijmegen)
  • Guillaume Salbreux (Francis Crick Institute)
  • Christina Scheel (Institute of Stem Cell Research, Helmholtz Center Munich)
  • Buzz Baum (Medical Research Council Laboratory for Molecular Cell Biology at UCL)

Also, all MECHANO·CONTROL consortium members will be attending the summer school and will be giving some of the workshops: Aránzazu del Campo (Leibniz-Institut für Neue Materialien, INM), Sergi Garcia-Manyes (King’s College London, KCL), Pere Roca-Cusachs and Xavier Trepat (Institute for Bioengineering of Catalonia, IBEC), Patrick Derksen and Johan de Rooij (University Medical Center Utrecht, UMCU), Marino Arroyo (Universitat Politècnica de Catalunya, UPC) and the companies NovioCell and Mind the Byte.

Consortium members at Saarbrücken meeting

Preliminary list of workshop topics:

  • Hydrogel mechanics
  • Design of tuneable gels
  • Biomechanical modelling
  • Breast cancer biology
  • Single molecule mechanics
  • Drug discovery

About MECHANO·CONTROL

TheMECHANO·CONTROL project is focused on the mechanical control of biological function.Mechanical forces transmitted through specific molecular bonds drive biological function, and their understanding and control holds an uncharted potential in oncology, regenerative medicine and biomaterial design.

MECHANO·CONTROL proposes to address this challenge by building an interdisciplinary research community with the aim of understanding and controlling cellular mechanics from the molecular to the organism scale. At all stages and scales of the project, it will integrate experimental data with multi-scale computational modelling to establish the rules driving biological response to mechanics and adhesion. With this approach, it aims to explore novel therapeutic approaches beyond the current paradigm in breast cancer treatment. If the partners can understand cancer biomechanics from the single molecule to the whole organ scale, they’ll be able to control mechanical forces to restore healthy cell behaviour and inhibit tumor progression.

Beyond breast cancer, the general principles targeted with this technology will have high applicability in oncology, regenerative medicine, biomaterials and many other biological processes and diseases.

MECHANO·CONTROL is a project funded by the European Commission, within the Future and Emerging Technologies (FET) proactive program.

Cadherin mechanotransduction in leader-follower cell specification during collective migration

A review article by Antoine A. Khalil and Johan de Rooij from UMC Utrecht have appeared in the Experimental Cell Research section of Elsevier

Collective invasion drives the spread of multicellular cancer groups, into the normal tissue surrounding several epithelial tumors. Collective invasion recapitulates various aspects of the multicellular organization and collective migration that take place during normal development and repair. Collective migration starts with the specification of leader cells in which a polarized, migratory phenotype is established.

Leader cells initiate and organize the migration of follower cells, to allow the group of cells to move as a cohesive and polarized unit. Leader-follower specification is essential for coordinated and directional collective movement. Forces exerted by cohesive cells represent key signals that dictate multicellular coordination and directionality. Physical forces originate from the contraction of the actomyosin cytoskeleton, which is linked between cells via cadherin-based cell-cell junctions.

The cadherin complex senses and transduces fluctuations in forces into biochemical signals that regulate processes like cell proliferation, motility and polarity. With cadherin junctions being maintained in most collective movements the cadherin complex is ideally positioned to integrate mechanical information into the organization of collective cell migration. Here we discuss the potential roles of cadherin mechanotransduction in the diverse aspects of leader versus follower cell specification during collective migration and neoplastic invasion.



Khalil, A.A., Experimental Cell Research, https://doi.org/10.1016/j.yexcr.2019.01.006

Iproteos, IBEC and VHIR to develop an innovative therapy against solid tumors

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.

Read more on the IBEC website.

Is the bottom-up approach enough to understand a whole system?

An opinion piece by IBEC group leader Xavier Trepat has appeared in the News and Views section of the current issue of Nature, which is devoted to ‘Bottom-up biology’.

In his piece ‘Bottom does not explain top’, Xavier argues that understanding how complex biological structures – or even entire cells – are built can only provide a certain amount of insight into how biological systems function at higher levels of organization. There are many variables such as density, or even pathologies suffered by the subject, that affect cell behavior at the mesoscale – that is, at the longer, more ‘system-level’ scale than that of the individual components of an organism. Cells in a group, for example, can sense or respond to external stimuli that an individual cell cannot identify.

Read more on the IBEC website