Project Stories: Interview with Samuel Pearson

Project Stories: Interview with Samuel Pearson

Samuel Pearson moved from Australia to Germany, where he works with research groups all over Europe with one common goal: to understand the factors influencing cancer progression. Samuel, Head of Applications in the “Dynamic Biomaterials” division of the Leibniz Institute for New Materials (INM), led by Prof. Aranzazu del Campo, is one of the Mechano·Control members. His work is focused on upscaling the production of polymer materials for 3D cell culture and bringing them towards commercialisation. Let’s take a closer look into his role within the consortium.

To understand how diseases like breast cancer develop, the response of breast cancer cells to different factors need to be studied one by one in isolation in 3D cultures. Samuel Pearson and his team produce synthetic hydrogels for 3D cell encapsulation with the possibility to adjust different parameters. These hydrogels mimic the properties of the natural breast cancer tissue in normal and disease conditions.

A particular interest of his group is the upscaling of the hydrogel precursors using affordable precursors and the design of stable, easy-to-handle compositions. This is the first step in technology transfer from the Mechano·Control project. With Mechano·Control partners, these materials are further developed into predictive breast cancer models.

Another crucial milestone for Samuel and his team is the processability of the hydrogels, which is related to the rate at which they are formed, i.e. the speed of the crosslinking reaction [1] during which cells are retained in a 3D matrix. The group has developed a patented crosslinking approach [2] based on thiol-methyl sulfone reactions which offer very convenient timescales for uniform encapsulation of cells. “In the future, we want to optimize our 3D cell encapsulation systems for automated high throughput methods that will enhance reproducibility and expand the applicability of our platform” explains Samuel. “The figure below shows how basal and luminal cells in breast cancer organoids organise in response to different adhesive ligands in the surrounding polymer network, which relies on consistent network properties” adds Samuel.


Figure 1: Invasive H7 breast cancer organoids were encapsulated in biofunctional hydrogels made from polymers developed at the Leibniz-INM. After 2 days of encapsulation, the effect of different bioactive ligands RGD and DGEA on polarization of the basal cells (stained with K14) and luminal cells (stained with K8) was explored. Scale bar = 50 um. Cell encapsulation and imaging were performed by Dr. Gulistan Kocer.

The materials developed by Samuel and his team play a crucial role in the Mechano·Control consortium. The high level of control and uniformity of the synthetic hydrogels allows to reduce the experimental variability in the biological studies, and this will help to uncover the individual factors that influence cancer progression. Moreover, this technology will not only be of great use for the consortium, but it also offers broad scientific and commercial potential for other 3D tissue culture models.

We are optimising polymer structure and crosslinking chemistry to make hydrogels with very reliable properties. The focus right now is upscaling to allow high throughput studies and moving towards commercialisation

Samuel Pearson

The Mechano·Control project brings together an interdisciplinary research community with the aim to understand and control how cells transmit and detect mechanical forces, from molecules to organs, and all the way up to the organism level. This requires developing and integrating disparate technologies, and each research group involved in the project is an expert in a very specific field and scale: “Each group has its own deep expertise, but because we are working towards a common goal everyone is really motivated to understand the contributions from the other partners, which deepens everyone’s knowledge and experience.”

VIDEO HERE


[1] A crosslink is a bond that links one polymer chain to another, forming a network. Hydrogels are crosslinked networks of hydrophilic polymers that are swollen with water and widely used for 3D cell culture. The crosslink density is a key parameter that determines the mechanical properties of the hydrogel, which can in turn influence the behaviour of encapsulated cells. In the research described above, covalent crosslinks are formed using a patented thiol-methyl sulfone crosslinking reaction.


[2] del Campo, A.; Farrukh, A.; Paez, J. I. Novel Hydrogels. WO2021001203A1, 2021, Priority DE102019117997A 2019-07-03, Filed 2020-06-23, Published 2021-01-07.

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.)

Mechano·Control featured at the “Future Tech Week” and “R&I days”

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).

Moreover, on September 22nd and 23rd, Future Tech Week will be part of the flagship European Research and Innovation Days event, within Hub 8 for the European Innovation Council.

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.

You can watch the session here

Pere Roca-Cusachs elected member of EMBO

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.

About EMBO:

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.

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.