Project Stories: Interview with Zanetta Kechagia

The Mechano·Control project aims to understand and control cellular mechanics from molecules to organs, and all the way up to the organism level. With this approach, its interdisciplinary research community will develop specific therapeutic approaches to tackle breast cancer. Zanetta Kechagia joined the Mechano·Control consortium from the first day that the project was launched. She is a postdoc in the team led by Pere Roca-Cusachs at IBEC, who is the principal investigator of the project.

Zanetta is focused on understanding the role of cell mechanics in the cellular and subcellular level. She is particularly interested on how extracellular matrix (ECM) composition and stiffness can jointly influence cell behaviour. “To achieve this, we are using a series of molecular and mechanical perturbations to unravel the role of specific cell-ECM interactions in shaping cellular mechanoresponses” explains Zanetta. 

Mammary gland epithelial cells. In cyan Intermediate filaments and red integrin β4. Scale bar: 20um (Picture by: Zanetta Kechagia)

Currently, she and other researchers at Roca-Cusachs’ lab are trying to identify which cell-ECM interactions can alter the mechanical properties of the cell cytoskeleton. To do so, she uses optical tweezers to perform oscillatory rheological studies, probing cytoskeletal mechanoresponses that are specific for different extracellular molecular components.

“We have found that cells respond to stiffness differently on different ECM substrates and that integrin molecules are key mediators of such responses. By using different ECM coatings, we can probe specific integrin interactions and record changes in the viscoelastic properties of the cytoskeleton over time.” – Zanetta Kechagia, PostDoc at IBEC

Mechanical forces greatly influence cell behaviour, for example in determining whether they differentiate, proliferate, or adopt a malignant phenotype. Understanding how molecular interactions can lead to changes in cell mechanical properties is a fundamental step in order to understand how mechanics control cellular behaviour and eventually tissue responses and cancer progression.

To meet this end, Zanetta is performing these experiments using breast epithelial cell lines with the aim to validate them at the organoid and tissue level, with the help of the other consortium partners. The Mechano·control project covers all scales, starting from single molecule nanotechnology at the smallest scale, to organoids and animal models at the organism scale to uncover cell responses to force at every scale.

Mechano·Control brings together very distinct but complementary research fields and scientists of the highest calibre in their respective fields. For Zanetta, joining the Mechano·Control project has been a great experience so far. “I had the chance to participate in several meetings, visit the partner institutions and discuss my work with our colleagues.  This helped me to acquire new knowledge and new research ideas to rise. One such exceptional experience was the summer school organised by Mechano·Control in 2019, where all the partners had the chance to exchange research ideas and present their work to an international audience.”

Mechano·Control featured at the Winter Issue of the EU Research Magazine

Mechano·Control featured at the Winter Issue of the EU Research Magazine

How do forces affect cell behavior? The Mechano·Control project is featured with a one page article in the EU Research Magazine in the “Winter’s Issue: Cellular and Molecular Biology research“.

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”

Pere Roca-Cusachs

“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.”

Pere Roca-Cusachs

You can read the article here:

We want to thank the EU Research Magazine for the article (EU Research WIN20/P17.)

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

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.

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)

Pere Roca Cusachs, Institute for Bioengineering of Catalonia (chair)
Xavier Trepat, Institute for Bioengineering of Catalonia (co-chair)
Marino Arroyo, Technical University of Catalonia-BarcelonaTech and Institute for Bioengineering of Catalonia (co-chair)

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.