With every movement we make, cells in our bodies exert, transmit, withstand and detect forces. These forces take place on different scales: in our molecules, tissues and organs, and in our bodies as a whole. But how exactly do these forces affect how tissues and organs behave?
The EU-funded project MECHANO-CONTROL was launched in 2017 to answer this question. Although there’s evidence that mechanical forces drive fundamental biological processes such as embryonic development, tumour growth and wound healing, scientists don’t yet know how this happens. Understanding how these forces work could open up new avenues in regenerative medicine, biomaterial design and, more importantly for this particular project, cancer research.
A novel approach in the war against breast cancer
Coordinated by the Institute for Bioengineering of Catalonia (IBEC), the MECHANO-CONTROL team are focusing their research on breast cancer. They’re currently in the process of investigating the role that hardness plays in the formation and growth of breast tumours.
IBEC researcher and project leader Dr Pere Roca-Cusachs explains in an interview
posted on Europa, the EU’s official web portal: “We started with the knowledge of the role of tissue mechanics in driving tumour progression: tumour tissues are stiffer than normal healthy tissues. But also, the stiffer the tumour, the faster it grows. So if making the tumour stiffer makes it grow faster, making it softer, or preventing the response to stiffness, might make it grow slower. That would mean that if we can find ways to prevent tissue stiffening, we might stop the further development of cancer – without chemotherapy and painful surgeries.”
If the team succeeds, this will mean good news not only for breast cancer sufferers. Their findings could have an impact on many other forms of cancer, too. For example, the project partners’ discovery that one particular protein (talin) unfolds and gets exposed to the binding of another protein (vinculin) only when cells apply forces on stiff tissues has led to a spin-off project to develop a drug that prevents this interaction that could block cell response to mechanical forces in tumour stiff tissues. Funded by the EU as part of the Future and Emerging Technologies Innovation Launchpad initiative, the TALVIN project
aims to develop a drug specifically for pancreatic cancer. “Whereas our compound has potential across several cancer types, we will focus on pancreatic cancer as it is highly associated with chronic pancreatitis and the corresponding fibrosis, which induces a dramatic stiffening of the tissue,” Dr Roca-Cusachs says.
A multidisciplinary toolkit
To unravel the mechanisms responsible for tissue stiffness, MECHANO-CONTROL is combining expertise from different fields. Biologists, biophysicists, engineers, modellers and chemists are all contributing their knowledge in fields ranging from single molecule nanotechnology on the smallest scale to organoids and animal models at the organism scale.
“In order to get answers, we are using a combination of cell biology and physical modelling,” Dr Roca-Cusachs says in another interview
posted on the ‘Journal of Cell Science’ website. “We started by looking into this mostly at the level of integrin-based adhesions. Now, we are also interested in what happens at the level of the nucleus and the plasma membrane. I think we are getting to some interesting conclusions on how mechanosensing [responsivity to mechanical stimuli] is regulated in these other nodes, which is less well understood.”
By gaining insight into the biomechanics of cancer from the single molecule to the whole organ, MECHANO-CONTROL (Mechanical control of biological function) will pave the way for new therapies across a wide range of diseases.
For more information, please see: MECHANO-CONTROL project website