The Power of Structure: What Makes Tissue Strong?

Interview with prof. dr. G.H. Koenderink

Prof. dr. Gijsje Koenderink onderzoekt bij de TU Delft hoe cellen en weefsels hun stevigheid en flexibiliteit krijgen. Haar werk richt zich op collageen, een belangrijk bouwmateriaal van het lichaam. Veranderingen daarin spelen een rol bij verschillende bindweefselaandoeningen waar ook Stichting Power of Reflection zich op richt.

Can you explain what collagen is?

“Collagen is a protein, or rather a whole family of proteins. The best-known type is collagen type I, which is found in the skin, for example. But there are also other types, such as type II in cartilage.
Collagen molecules form fibers, and those fibers in turn form networks. These collagen fiber networks largely determine the properties of a tissue. In the skin, for example, the fibers are arranged in many different directions, allowing the skin to move in all directions. In tendons, however, they are neatly aligned in one direction because they are mainly subjected to tensile forces. I find it fascinating how the body adapts this structure to the function of the tissue. Cells essentially build their own ‘environment’ and do so in a way that suits what the tissue needs to be able to do.”

Is all of that determined by DNA?

“DNA certainly plays a role, but it is not the whole story. All the cells in our body have the same DNA code, yet they perform different functions. That is because cells respond to their environment and to what they ‘experience.’ A good example is how tissues adapt to mechanical loading. If you start moving more or exercising, not only does your muscle mass change, but the structure of your connective tissue and even your bones changes as well. The body is constantly adapting.”

What is the focus of your current research?

“A major part of our research is aimed at understanding how these mechanical properties arise. What makes a tissue stiff or, conversely, flexible? We study this at different levels: the collagen molecule itself, the fibers that form from it, and the network those fibers create together. What we have found is that the structure of the network is the main factor determining the properties of a tissue. Only when a tissue is deformed very strongly do the properties of the fibers or proteins themselves begin to play a significant role.”

How do you investigate that?

“In the laboratory, we often work with collagen models. For example, we create collagen fibers from purified collagen. This gives us a simpler system without cells, making it easier to understand what is happening.
Real tissues, of course, are much more complex. They also contain cells and other molecules, such as hyaluronic acid. The combination of these ingredients ultimately determines how a tissue behaves. That is why we try to add increasing levels of complexity to our models step by step. And for the past several years, we have also been measuring real tissues, for example in collaboration with Erasmus MC.”

How do such measurements work?

“We measure, for example, how stiff a tissue is. We do this by pressing on a cell or a small piece of tissue with a very tiny needle. This allows us to see how the material responds. With these measurements, you can compare healthy and diseased tissue. We have done this, among other things, with liver tissue, where we found that tumor tissue is stiffer than healthy tissue. Such differences are interesting not only for diagnostics, but also because cells themselves respond to mechanical properties.”

Can cells actually ‘feel’ that?

“Yes. It is only relatively recently that we have learned that cells respond not only to chemical signals but also to their mechanical environment. If a tissue becomes stiffer than normal, cells may start behaving differently. In some cases, this can contribute to disease processes, such as cancer or fibrosis. This young field is called mechanobiology: the study of how mechanical properties influence biological processes.

In the past, researchers usually cultured cells on hard surfaces, such as glass slides. We now know that this is often an unnatural environment. Cells behave very differently when placed on a surface that more closely resembles their natural surroundings. Brain cells, for example, are best cultured on a soft surface because our brains are soft as well.”

Do you also conduct research into collagen-related connective tissue disorders?

“No, unfortunately not yet, because we need funding for that. We did submit a grant application to study cartilage cells from patients with Ehlers-Danlos syndrome, but unfortunately it was not funded.
What we would really like to do is systematically investigate how collagen structure changes in collagen-related connective tissue disorders. Is there more or less collagen? Are the fibers built differently? And what does that mean for the mechanical properties? These kinds of questions fit very well with what we do, but they require collaboration and resources. We are biophysicists, so we bring certain techniques and insights, but you also need access to patient material and clinical expertise. That is why we are increasingly collaborating with partners such as Erasmus MC. We hope to expand those collaborations further.”

Do you think your field can contribute to new treatments?

“Yes, I certainly do. We are now seeing the field develop toward what is sometimes called mechanomedicine . This approach examines whether it is possible to intervene in disease processes through the mechanical properties of tissues. In cancer research, for example, scientists are investigating whether tissue stiffness can be altered by breaking down certain tissue components. This turns out to be complex, but there are promising first steps. Researchers are also exploring how mechanomedicine can be used to repair tissue or stimulate the growth of new tissue. It is still far from routine clinical practice, but it is a new and interesting perspective that is receiving increasing attention.”

What are your hopes for the future?

“Ik hoop dat we meer verbinding kunnen maken tussen fundamenteel onderzoek en medische toepassingen. Kennis over algemene principes van collageen kun je vaak ook in andere contexten gebruiken. Initiatieven die onderzoekers met elkaar in contact brengen, zoals de stichting Power of Reflection doet, kunnen daarom echt helpen.”

The Power of Structure: What Makes Tissue Strong?

Written by: Diana de Veld, science journalist