Yixuan Li (promotion date: 11 November 2009)

Linking particle dynamics to intercellular micromechanics in living cells

Promotion date: 11. November 2009

Promotor: Prof. Dr. Frieder Mugele

Assistant Promotor: Dr. Michel Duits

Main goal of this thesis was to access the capability of intracellular particle tracking (IPT) to generate new insights about micromechanical environments, of different intracellular probes inside the living cells, as well as methods for cellular heterogeneity analysis.

The use of IPT was explored further, to characterize cancer cells as being malignant or benign, based on their mean square displacements (MSDs). The analysis was applied to both pancreatic and breast tumour cells. MSDs amplitudes were higher in malignant cells. This illustrates the utility of IPT, to provide a semi-quantitative measure of the stiffness and active remodelling of tumour cells.

In comparison, AFM was employed to reveal the apparent elastic moduli of the malignant breast tumour cells. These were significantly lower than for the benign ones. However, for the pancreatic cells the moduli of benign and malignant cells could not be distinguished. This illustrates the value of IPT as a complementary nano-mechanical technique.

Bio-nanotechnology is quite a new field. How did you develop this special interest?

Measuring the response of cells to mechanical stress is a new approach indeed. Human endothelial cells for example, possess superb properties to withstand the blood pressure and shear stress. Another example found, is the metastatic nature of some tumour cells. Bio-nanotechnology is a fascinating multidisciplinary technology, that bridges: physics, chemistry, biology and engineering.

I performed my master thesis at Dresden University, studying the interaction between DNA and carbonated tubes. When coming to Twente, I experienced quite some difficulties in the project since no biological or physical background in cell mechanics was available in this group. My limited knowledge of physics and mathematics seemed a big obstacle. Also, it has been a hard time to learn all kinds of physical terms and communications. Gladly, I experienced a lot of support from my supervisors and colleagues.

Studying such a new field is interesting both from the fundamental and the application oriented point of view. On one hand, it connects the real-time mechanical change to the biological modification inside living cells, and opens new possibilities in addition to the traditional biological techniques.

On the other hand, it gives insight into the fundamental cell mechanical studies, about the interpretation of results offering more fundamental and systematic analysis, based on single particle dynamics.

In Europe, not so many groups are working on cell mechanics in-vivo system. It has been a challenge to connect the in-vivo and in-vitro studies in this filed, and due to the complicated behaviour of the cells, the interpretation of results is quite a challenge to us as well. Gladly, in the end, we achieved four publications in peer-reviewed journals.

Did you work together with different groups?

The collaboration with Münster University was a great success. They generously offered me the tumour cell lines and open discussions. Our joint paper, about using intracellular particle tracking as a tool for tumour characterization, will be published in the Journal of Biomedical Optics in soon.

And I received lots of help in the Biophysics Engineering and Polymer Biomaterials group, at the University of Twente.

Can nano-medicine be a new research topic for Mesa+?

I really think it would. In my opinion some breakthroughs are under way. Working on new generations of techniques for medical screening, diagnostics and therapy, is fascinating. For example nano-machinery can migrate through blood vessels. Some dreams can come true some day in this field. I strongly believe so.

What are your future plans?

A stable academic position would be great, of course. However, I think applying in industry is a safer way. It all depends on the opportunities. I don’t have management ambitions. I would like to contribute to bio-nanotechnology & nano-medicine in the future.