The described project is the first innovative demonstration of understanding the coupling between mechanical properties of cells and formation of metastases in organism on a biophysical, quantitative base. Thus, the project involves the collaborative work between different disciplines, namely biophysics (mechanical measurements), biochemistry (bioactive lipds) and medicine (clinicalconsequences).Yet, mechanical effects and its consequences for metastases formation in organisms have not beenconsidered. However, first observations made by the lab in Heidelberg in collaboration with theWeizmann Institute of Science (Israel) and the Clinical University Ulm (Germany) show convincingly that structural consequences upon cellular cytoskeleton (which is responsible for cellular mechanics)are involved in medical relevant processes. Thus, Sphingosylphosphorylcholine (SPC, a bioactivelipid) was found to cause structural changes in the cytokeration organization of epithelia cancer cells from the pancreas. Interestingly, SPC is more dominantly expressed by patients who suffer frompancreas tumours and who already distributed metastases in the body than with patients who havepancreas tumours but no formation of metastases, yet. Thus, SPC must provide a biochemical signalfor metastases formation by reorganizing the cytokeration assembly in cells. Its mechanicalconsequences for cells and for the formation of metastases from pancreas tumours is objective of thisproposal.Viscoelasticity of single cells will be determined with the single cell puller on top of an opticalmicroscope a technique established in Heidelberg. We will visualise cytoskeleton structure andmeasure viscoelasticity of Epithelial cells from the pancreas under various biochemical treatment. Thiswill enable us to define mechanical connectivity of various filament systems in cells which is supposedto play a major role in formation of metastasis.
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