Nanoscale structural and mechanical properties of α-synuclein amyloid fibrils.
Atomic force microscopy studies
Promotion date: 16. May 2012
Promotor: Prof. dr. ir. Vinod Subramaniam
Co-promotor: Dr.ir. Martin Bennink
In this thesis are studied: the structural and mechanical properties of amyloid fibrils formed by the human α-synuclein protein, associated with Parkinson’s disease. AFM is capable of performing both morphological and mechanical analysis on the fibrils. Especially the mechanical properties of the fibrils are becoming increasingly interesting from a nanomaterials point of view.
•the influence of the surface on morphological and mechanical properties;
•interaction between the fibrils and supported lipid bilayers using morphological, mechanical and affinity parameters;
•environmental influences, like different buffers, to get a more detailed understanding of structural characteristics.
Newly-developed surface property mapping techniques like Peakforce QNM and HarmoniX are used. These techniques use much higher frequencies to perform the indentation curves and to create higher data throughput.
What were the challenging aspects of your thesis project?
For example, the fibrils are about ten nanometer in diameter. At this scale performing measurements is quite demanding. For example gravity forces are less pronounced compared to other interactions, giving way for electrostatic forces to be dominant.
Using different types of atomic force microscopy together with new techniques, the way to perform measurements successfully on this highly important fibrils, are becoming more and more clear now. Also some models are suggested concerning stiffness, electrostatic properties and geometry involved.
Insight in these properties can contribute in the end in understanding how damaging aggregation of proteins associated with Parkinson’s disease evolve. Much of that process is still unknown. Different approaches solving this are under investigation. I hope my approach – of which I investigated some of the fundamentals – will contribute to this in the future.
How did you develop yourself as a researcher in these four years?
Managing a process like this in a four-year period, is quite complicated, especially as one has no experience at all in comparative projects. This makes PhD’s projects quite unique, I believe.
In the beginning the process is explorative, finding the exact core of the matter. As the project proceeds further, the strategic decisions are different. Then the question arises which experiments to choose to gather the most meaningful results in the time given. In the whole process the role of the supervisors is crucial, though one manages the project in an independent way.
Also I liked accompanying students in education and experiments very much. Helping them to build up new skills is very rewarding.
What are your future plans?
Right now, I am working as a mechatronic systems engineer at Demcon, a spinoff company of the University of Twente, specialized in designing mechatronic systems in various fields and modes of application, especially high-tech and medical devices. My function is a combination involving research and project management tasks.
My biomedical background together with skills developed in this project and in mechatronics, now come together very nicely for me. I am enjoying the dynamic atmosphere in the commercial setting as a contrast to the thesis work in the last four years.
Did you feel part of the Mesa+ society?
The Nanobiophysics group is member of Mesa+ as well as the Mira institute, so that was a little mixed so to say. I enjoyed the Mesa+ day and the colloquia. Also the use of equipment and the outstanding support, for example by Frans Segerink, was very important for my project.
Did you have some nice publications?
Some are still underway, however already published articles are in: Nanoscale Research Letters, Journal of Physics and Condensed Matter, Soft Matter and ACS Nano.
What, in your opinion, is important for Mesa+ to stay successful in future?
Organising events like the Mesa+ day, is important to encourage people to set up joined projects in an easy way, feeling free to step in on one another.
The way Mesa+ facilitates spinoff companies is a unique feature of the institute that should be cherished. This is of international importance as it is on a national level and for the region of Twente in the east of the Netherlands. As a member of the Demcon company, I come across spinoff companies regularly. That is a nice feeling.