Cell motility has been found to play a role in many important body functions as well
as the embryogenenis of mulitcellular organisms like vertebrates. From a physics
point of view the interesting questions behind every motion are: Why is it moving?
Where do the forces come from?
Today we know that the motility of many cells is dependent on an active polymer
network. Actin, one of the most abundant proteins in the body, is constantly polymerized,
being moved around and depolymerized in motile cells. Until now, only
forces outside the cell like traction forces could be measured. The direct measurement
of the force generated by polymerizing actin filaments has only been measured
by our lab and the lab of M. Radmacher. In these measurements fish keratocytes
were used. Whereas I did these experiments, for the first time, on mammalian cells.
To measure forward forces on neuronal growth cones I stabilized the SFM, as
measurement times went up from minutes to hours. Furthermore measurements
had to be performed at 37°C instead of room temerature, this induced drifts of the
substrate. I incorporated an optical trap into the microscope to track the motion
of the substrate. A feedback loop moved the SFM cantilever to minimize relative
motion of substrate and cantilever.
For keratocytes I directly measured the forces produced by actin polymerization
and, to my knowledge for the first time, the forces associated with the retrograde
actin flow using a SFM. The result was that both actin and myosin play important
but different roles in motility. For actin it turned out that considering just the polymerization
was not enough. Actin depolymerization and the resulting entropic forces
are a completely new physical effect in actin based cell motility. With this new force
in the force balance I can explain all effects observed in my experiments without introducing
any new biochemical feedback loops.
Finally I showed that neuronal growth cones are very soft and weak structures.
They are at least one order of magnitude softer and weaker as for example fibroblasts
or cells forming the blood vessel walls. As neurons are usually located in soft
environments this does not impede their normal outgrowth. It could even serve as a
safety mechanism that prevents cell from growing into wrong areas like breaching
the blood-brain-barrier, on a physical level. For a neuron the wall of a blood vessel
feels like a brick wall for us.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-124097 |
| Date | 25 September 2013 |
| Creators | Fuhs, Thomas |
| Contributors | Universität Leipzig, Fakultät für Physik und Geowissenschaften, Prof. Josef A. Käs, Prof. Josef A. Käs, Prof Paul A. Janmey |
| Publisher | Universitätsbibliothek Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis |
| Format | application/pdf |
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