From Single Molecules to Collective Phenomena - The Origin of VWF-Induced Collective Networks
Final Report Abstract
Blood clotting and blood clotting disease are not a simple problem of genetics. As trivial as this may sound on first sight the harder it is to fill this statement with actual facts. We have managed to gain fundamental insight in the role of hydrodynamics and physics in general for the activation of the blood clotting process. We have found the phenomena of reversible network formation and have developed a semi analytical model to explain these effects based on the competition of two timescales. Since one timescale (binding) origins rather from molecular states and the other from hydrodynamics (inverse shear rate) these model manages to relate changes on the molecule with changes in the macroscopic behaviour under flow. We further elaborated how RBCs (haematocrit) the most prominent “particle” of blood affects the events of aggregate formation and adhesion of platelets. All this was the combined effort – from the get go – of theory, experiment and technology of an interdisciplinary team of scientists and couldn’t have been done any other way. For the future, the role of rotation in flow that has been mostly neglected for the blood clotting event before our studies, may become particularly important. For example for the formation of complete stenosis we hypothesize the following scenario: When arteriosclerosis for instance begins to narrow the vessel, shear and rotational flow increases which triggers stretching and wrapping of platelets. If the plague now breaks, blood will be exposed to collagen, which impairs the composite of platelets and vWF to disintegrate reversibly. The composite will rather be “fixed” against the wall of the damaged vessel. This may be a if not the crucial event during stroke. We will follow up on these ideas as well as new concepts of cell signalling that have seen fruitfully stimulations from some groups of the research unit SHENC.
Publications
- A Novel Tool for Dynamic Cell Adhesion Studies - the De-Adhesion Number Investigator DANI. Lab Chip 2013, 14 (3), 542–546
Hartmann, A.; Stamp, M.; Kmeth, R.; Buchegger, S.; Stritzker, B.; Saldamli, B.; Burgkart, R.; Schneider, M. F.; Wixforth, A.
(See online at https://doi.org/10.1039/c3lc50916h) - Blood-Clotting-Inspired Reversible Polymer-Colloid Composite Assembly in Flow. Nat. Commun. 2013, 4, 1333
Chen, H.; Fallah, M. a; Huck, V.; Angerer, J. I.; Reininger, A. J.; Schneider, S. W.; Schneider, M. F.; Alexander-Katz, A.
(See online at https://doi.org/10.1038/ncomms2326) - Circulating but Not Immobilized N-Deglycosylated von Willebrand Factor Increases Platelet Adhesion under Flow Conditions. Biomicrofluidics 2013, 7 (4), 44124
Fallah, M. a.; Huck, V.; Niemeyer, V.; Desch, a.; Angerer, J. I.; McKinnon, T. a. J.; Wixforth, a.; Schneider, S. W.; Schneider, M. F.
(See online at https://doi.org/10.1063/1.4819746) - Hematocrit and Flow Rate Regulate the Adhesion of Platelets to von Willebrand Factor. Biomicrofluidics 2013, 7 (6), 64113
Chen, H.; Angerer, J. I.; Napoleone, M.; Reininger, A. J.; Schneider, S. W.; Wixforth, A.; Schneider, M. F.; Alexander-Katz, A.
(See online at https://doi.org/10.1063/1.4833975) - High Shear Dependent von Willebrand Factor Self-Assembly Fostered by Platelet Interaction and Controlled by ADAMTS13. Thromb. Res. 2014
Kragh, T.; Napoleone, M.; Fallah, M. A.; Gritsch, H.; Schneider, M. F.; Reininger, A. J.
(See online at https://doi.org/10.1016/j.thromres.2014.03.024) - The Various States of von Willebrand Factor and Their Function in Physiology and Pathophysiology. Thromb. Haemost. 2014, 3 (16), 1–12
Huck, V.; Schneider, M. F.; Gorzelanny, C.; Schneider, S. W.
(See online at https://doi.org/10.1160/TH13-09-0800) - A Surface Acoustic Wave-Driven Micropump for Particle Uptake Investigation under Physiological Flow Conditions in Very Small Volumes. Beilstein J. Nanotechnol. 2015, 414–419
Strobl, F. G.; Breyer, D.; Link, P.; Torrano, A. A.; Bräuchle, C.; Schneider, M. F.; Wixforth, A.
(See online at https://doi.org/10.3762/bjnano.6.41) - Protons at the Speed of Sound: Predicting Specific Biological Signaling from Physics. Sci. Rep. 2016, 6 (March 2015), 22874
Fichtl, B.; Shrivastava, S.; Schneider, M. F.
(See online at https://doi.org/10.1038/srep22874) - Surface Deformation during an Action Potential in Pearled Cells. Phys Rev E 2017, 52406 (96), 1–8
Mussel, M.; Fillafer, C.; Ben-porath, G.; Schneider, M. F.
(See online at https://doi.org/10.1103/PhysRevE.96.052406) - On the Physical Basis of Biological Signaling by Interface Pulses. Langmuir 2018, 34, 4914–4919
Fichtl, B.; Silman, I.; Schneider, M. F.
(See online at https://doi.org/10.1021/acs.langmuir.7b01613)
