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WCMM fireside chat: Vinay Swaminathan

Vinay by one of his microscopes. Picture.
Vinay in his natural environment. Photo by Faculty of Medicine, originally published by Johanna Sandahl.

Welcome to another WCMM Fireside Chat, a series of articles dedicated to highlighting the work of researchers within and around the WCMM in Lund to promote collaboration and communication.

This time we present our discussion with Vinay Swaminathan, a group leader at WCMM focused on cell mechanobiology. We talked about his work, the successes and challenges of multidisciplinary science and the collaborative environment at the WCMM and in Lund. Enjoy!

Understanding cells in their proper place

Vinay’s group works on untangling how cells sense their physical environment and respond accordingly. Cells, after all, do not just passively sit in a neutral space, but both interact with and are affected by the many parallel signals in their surroundings. These include both biochemical signals, as well as physical properties of the environment.

I always say: If you want to fix a car, you first need to learn how the car works.

While his interests are firmly rooted in basic cell biology, the work has implication for major clinical challenges such as cancer, where stiffness has been found to drive cancer progression and complicate treatment. Understanding these changes may one day help us to tackle the root cause of cancer pathogenicity and disease resistance. On top of that, tissue stiffness plays a role in tissue regeneration, development and other important processes.

Basic science is at the core of every scientific discovery, and for me, personally is the most exciting aspect, because of its focus on the nuts and bolts, in mechanisms and asking questions such as Why and how.

Microscopy images of cells exposed to different environments. Figure.
In all above examples, physical cues from the extracellular matrix alone caused drastic changes in cell structure and behavior.

Mechanics meets biology

Vinay started with bachelor’s and master’s degrees in mechanical engineering, with an interest in the gritty details of engine building. This turned out to involve a lot more fluid dynamics and other aspects which he found less appealing, so he pivoted with his master’s thesis project into the mechanics of mosquito bites. This drew him into the new field of biomechanics and led to a PhD in materials science and microscope design. During the PhD, Vinay sometimes found himself lacking biological questions to answer with the new tools he was creating which additionally stimulated his interest in biology. Finally, during his postdoc, combined microscopy and cell biology with his engineering background.

We would build microscopes, and then ask people to use them without really knowing what the biological question is. It's always bad when you build a hammer, and then you are looking for a nail.

Successes, challenges, and the future of mechanobiology

As one of his proudest achievements, Vinay highlighted a paper he co-authored with his sister, who was a cancer biologist interested in cell migration and growth factor signaling. Using a system that Vinay and his group developed, they characterized an important relationship between mechanical properties and how metastatic cancer cells are, which has since spawned a small research field, with many other labs working the question

While it's always good to be motivated by trying to find a cure, or solving a disease, that's not how advance happens. Basic science is at the core of every scientific discovery and the most exciting aspect is that you really are investigating, you're doing hardcore research and trying to identify by mechanisms.

Physical forces influence the metastatic nature of cancer cells. Figure.
Physical forces influence the metastatic nature of cancer cells. Figure adapted from Butcher et al., 2019, Nature Reviews Cancer.

As for the biggest challenge in the field, Vinay highlighted decades of knowledge obtained from 2D cell culture on flat plastic dishes, which now must be partially un-learned in light of new 3D culture systems which better replicate natural biological environments. How to approach and adapt methods to these new ways of growing cells and how to integrate previous knowledge with the new, is an ongoing point of discussion. Another unsolved question is how exactly mechanical changes result in changes on the epigenetic level and how this in turn influences the cell.

Vinay divides his  interests into 1) the molecular mechanisms that allow cells to sense their surroundings, 2) the organization of epithelia and similar structures based on environmental cues and 3) the application of this knowledge to 3D environments such as organoids, spheroids and in vivo systems. The last point in particular, is where sees his research in the long term. Another aspiration of Vinay’s is to answer one of the unsolved questions mentioned above - to better understand how mechanical clues affect the epigenome, instill cellular memory or influence differentiation.

Importance of collaborative research

Mechanobiology is a classic example of interdisciplinary science. Vinay works with many different local and international institutions, for example NanoLund, the Niels Bohr Institute in Copenhagen, and of course the Biomedical Center (BMC) itself. The WCMM in Lund helps to bring together people with very different expertise. In Vinay’s case, his group is often the one providing help and training for colleagues looking for state of the art, high resolution or super resolution imaging. At the same time, he highlighted many productive collaborations within the center, such as with Darcy Wagner, Paul Bourgine, Filipe Pereira and Nick Leigh. Aside from the WCMM, the Lund University Cancer Center is another of his affiliations through which he looks for collaborations in cancer biology, where mechanobiology plays an important role.

I think that you have to collaborate if you want to do science efficiently, effectively, and well. And that means that you need people who have the expertise to contribute to every piece of science that comes out. One lab is not capable, in the modern day, of generating all that is needed for a good scientific work.

Overall, Vinay considers Lund a positive research environment for fostering collaboration, particularly due to organizations and events that bring together researchers from different backgrounds. Making these opportunities a daily occurrence by concentrating interdisciplinary research in a single building would, he suggests, take Lund a step further as a collaborative environment.