31 March, 2021
Wellbeing and medical health is generally seen as the realm of biology rather than physics. But physics biology collaborations are forging a new field – mechanobiology – a research area key to understanding health and disease.
We’re familiar with the idea of chemical messaging: we know neurotransmitters pass messages to nerves, and that hormones travel through blood to signal to cells throughout the body. But it’s less well known that our cells are also constantly reading and reacting to mechanical signals. MacDiarmid Institute Principal Investigator and Massey University Professor Bill Williams says that this is exactly what the new field of mechanobiology studies.
“Cellular mechanobiology looks at the physical structure of cells and their environments, and the role that mechanics plays in sensing and actuation.”
We tend to associate ‘mechanics’ as something more on the size-scale of our cars, but it’s micro-mechanics that he’s talking about. The ‘extracellular matrix’ surrounding our cells is a protein-based scaffold, an example of which is connective tissue. This matrix can vary in stiffness (much like the difference between fresh or stale bread). It turns out that the stiffness of the matrix has a big effect on the ability of our cells to function healthily and withstand disease. Changes in the stiffness of this matrix are thought to contribute to many types of disease, including cancer.
“Changes in the materials properties of this extracellular matrix around our cells for example can be transmitted through the cell membrane and
into the cytoplasm where they can impact on gene expression”. Professor Williams says mechanobiology is hugely multidisciplinary, encompassing cell biology, bioengineering and biophysics, and requires more than one measurement technique.
“If I gave you a slinky and asked you to measure the mechanics of the spring in different ways, all the measurements would report pretty much the same thing. But biological systems are typically spatially heterogenous and have mechanical properties that vary according to length and time scales. Typically you’re measuring something slightly different in when you apply a different technique.”
He says that developing a suite of techniques for the measurement of the mechanical properties of soft biological materials has been a recurrent theme throughout the history of the MacDiarmid Institute, and that the Institute is now well positioned with an impressive range of techniques including Optical Tweezers (his own research), AFM (Associate Investigator Dr Jenny Malmström), Microaspiration (Principal
Investigator Associate Professor Geoff Willmott), and Micropillar bending (Principal Investigator Associate Professor Volker Nock)
to address challenging problems.
Cancer tissues for example can be up to ten times stiffer than healthy tissues. So for cancer it’s important to measure the cell’s materials properties – and since these are complex, we need to have several techniques up our sleeve.Professor Bill Williams Principal Investigator Massey University
He points out that the mechanobiology field is by definition extremely collaborative. One key collaboration came about by chance, from a tearoom discussion with Dr Tracy Hale from Massey University’s School of Fundamental Sciences.
“We were chatting over a cup of tea, as you do, and I was talking about how we were working on bringing together several different techniques to measure the physical properties of cells. I mentioned that we were concentrating our efforts on standard cell samples in order to develop the techniques. But we needed an actual biological problem.”
And it turned out that Dr Hale had managed to produce a line of breast cancer cells lacking in a particular protein (heterochomatin protein 1) – a protein that is found to be expressed less in the most invasive cancer cells. The hypothesis was that the downregulation of the protein affects the mechanics of the cell nucleus in a way that impacts on their ability to migrate through the body.
“She had managed to grow cells like that, along with a control cell line, and was actually looking for biophysical materials scientists to work with.”
But why should we be doing this research here in NZ?
“It’s part of a responsible society that we put tax $ into science and medicine. And for that we need to be doing these things demonstrably at a world-class level. And yes there are big groups in the States doing this, but there’s lots of competition between those groups. New Zealand is small enough that we can collaborate effectively – this type of collaboration is an example of the strength of a Centre of Research Excellence like the MacDiarmid. Although each of the three techniques we’re using can be done elsewhere, first up, we’re as good as anyone else is, and secondly, unlike them, we’re all working together.”
His MacDiarmid Institute collaborators on the breast cancer cell work include University of Auckland Associate Professor Geoff Willmott, as well as PhD students Susav Pradhan and Ankita Gangotra (who has just left NZ for a postdoc in the USA). And Research Assistant Ayelen Tayagui from University of Canterbury Associate Professor Volker Nock’s lab has recently travelled to Auckland and Palmerston North to investigate the mechanics of fungal like organsims.
Professor Williams says that having already built up collaboration on the different mechanical measurements we can do within the Institute, we can now apply these more generally to other biological systems. “Volker’s been using his expertise in lab-on-a-chip force measurement to study the forces involved in the protrusion of hyphae of fungi (studying Myrtle Rust and Kauri Dieback).
The investment the Institute has already put in developing these techniques, calibrating and understanding them, means we can do exactly the right measurements.Professor Bill Williams Principal Investigator Massey University
"And now, with the help of Dr Hale, we can apply these to something else – these breast cancer cells – in fact anything that involves mechanical
properties of cells.”
For now the MacDiarmid Institute teams have the mechanical properties of breast cancer cells firmly in their headlights, using multiple physics techniques to better understand the biological environments that keep us healthy.