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Contributed Talk, Friday, 17:15 – 17:30 |
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Investigating the Mechanics
Behind Cellular Compartmentalization and Tumor Spreading
Steve Pawlizak, Anatol Fritsch,
Mareike Zink, Josef A. Käs
University of Leipzig, Faculty of
Physics and Earth Sciences, Institute of Experimental Physics I, Soft Matter
Physics Division, Linnéstraße 5, 04103 Leipzig, Germany |
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Contact:
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The development of cancer can be roughly divided into two characteristic
stages: In its early developmental stage, the tumor is confined to the
compartment of its origin. Only in the later stage, some tumor cells acquire
the ability to overcome the compartment boundaries and invade adjacent
tissue, which is called metastasis. This raises the question, what
is the reason for the new much more aggressive behavior? What makes these
metastatic tumor cells so special?
We investigate this unresolved problem from a biophysical point of
view. It seems obvious that something in the mechanical properties of these
cells must have radically changed [1]. A common model system is used to
demonstrate the process of compartmentalization: Two different populations
of suspended cells are mixed together. After a certain time, this mixture
will eventually segregate into two phases, whereas mixtures of the same
cell type will not.
In the 1960s, Malcolm
S. Steinberg formulated the so-called differential adhesion hypothesis
which explains the segregation in the model system and the process of compartmentalization
by differences in surface tension and adhesiveness of the participating
cells [2].
We are interested in to which extend the same physical principles affect
tumor growth and spreading between compartments. For our studies, we use
healthy and cancerous breast cell lines of different malignancy as well
as primary cells from human cervix carcinoma. We apply a variety of techniques
to study their cellular mechanical properties and interactions: The Optical
Stretcher is used for quantifying the global elastic properties of
single cells [3]. Cell-cell-adhesion forces are directly measured with
the help of a modified scanning force microscope. The combination
of this technique together with 3D segregation experiments in droplet
cultures might help to clarify whether or not surface tension is a
necessary – or even sufficient – factor to characterize tumor spreading.
[1] |
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A. Fritsch, M. Höckel, T. Kiessling,
K. D. Nnetu, F. Wetzel, M. Zink, J. A. Käs: Are
biomechanical changes necessary for tumour progression?, Nature
Physics 6 (10): 730–732 (2010). |
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[2] |
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R. A. Foty, M. S. Steinberg: The
differential adhesion hypothesis: a direct evaluation, Dev. Biol.
278 (1): 255–263 (2005). |
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[3] |
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J. Guck, R. Ananthakrishnan, H. Mahmood,
T. J. Moon, C. C. Cunningham, J. Käs: The
Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells,
Biophys. J. 81 (2): 767–784 (2001). |
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