Current research / employment

The migration of single cells through the extracellular matrix (ECM) of tissue plays a key role in organ development, wound healing and the progression of metastatic cancer. Cell migration behavior is studied in the laboratory mostly on rigid 2D substrates. Living cells in the body, however, need to migrate through the dense 3-dimensional network of the ECM. It is unclear how cells are able to migrate through such a network: do they squeeze through existing pores, deform the ECM to open up holes, or simply digest obstructing fibers?

In my PhD project, I study cell migration through artificially reconstituted tissue by simultaneously imaging living cells together with the three-dimensional tissue structure using time resolved 3D confocal microscopy. I have investigated new ways to tune the structure and stiffness of artificial tissue, developed image processing tools to characterize their 3D morphological properties, and applied these tools and techniques to study cell migration. For instance, neutrophil granulocytes are thought to reach sites of inflammation by squeezing through existing openings in the dense ECM network. To understand if certain size pores facilitate or hinder the locomotion of neutrophils, I develop algorithms to identify pores, quantify their sizes and map their connections. I image migratory paths of neutrophils under varying conditions and correlate preferential direction and local pore size distribution. Another migration strategy, utilized by fibroblasts, is to anchor onto fibers and create high pulling forces to actively overcome the steric hindrance presented by the ECM. When a cell pulls on a fiber, the fiber undergoes deformation that can be quantified through image tracking. If the mechanical network behavior is known, the forces exerted by the cell can be estimated. However, this has not yet been achieved. To find an appropriate mechanical model, we have used visual analysis of thermal vibrations to quantify the stiffness of single fibers, mimicked local network deformations by pulling with a known force on magnetic beads, and applied global shear deformation to trace the individual strains of fibers. These studies were done in close collaboration with researchers at Harvard University. We are now able to better understand the local environment of migrating cells, and can relate changes in the migratory behavior and strategy of certain cell types to the structural as well as mechanical properties of the tissue.

Figure: 3D visualisation of the spatial structure of a collagen gel (red). On the right half of the image, computationally detected pores of the gel are represented as green spheres.

Publications A.T. Krummel, S.S. Datta, S. Münster, D.A. Weitz, Visualizing Multiphase Flow and Trapped Fluid Configurations in a Model Three-Dimensional Porous Medium, AIChE Journal, 59(3), 1022–9, (2013)

S. Münster, L.M. Jawerth, B. Fabry, and D.A. Weitz, Structure and mechanics of fibrin clots formed under mechanical perturbation, Journal of Thrombosis and Haemostasis, 11(3), 557-560, (2013)

S. Münster, B. Fabry, A Simplified Implementation of the Bubble Analysis of Biopolymer Network Pores, Biophysical Journal, 104(12), 2774-5, (2013)

S. Münster, L.M. Jawerth, B.A. Leslie, J.I. Weitz, B. Fabry, and D. A. Weitz., Strain history dependence of the nonlinear stress response of fibrin and collagen networks, PNAS, 110(30), 12197-12202, (2013)

Y.I. Heit, P. Dastouri, D.L. Helm, G. Pietramaggiori, G. Younan, P. Erba, S. Münster, D.P. Orgill, S.S. Scherer, Foam Pore Size is a Critical Interface Parameter of Suction-Based Wound Healing Devices, Plastic and Reconstructive Surgery, 129(3), 589-97, (2012)

T.M. Koch, S. Münster, N. Bonakdar, J.P. Butler., B. Fabry, 3D Traction Forces in Cancer Cell Invasion , PLoS One, 7(3), e33476, (2012)

C.P. Broedersz, K.E. Kasza, L.M Jawerth, S. Münster, D.A. Weitz, F.C MacKintosh, Measurement of Nonlinear Rheology of Cross-linked Biopolymer Gels, Soft Matter, 6(17), 4120-7, (2010)

L.M. Jawerth*, S. Münster,* D.A Vader, B. Fabry, D.A. Weitz, A Blind Spot in Confocal Reflection Microscopy: The Dependence of Fiber Brightness on Fiber Angle in Imaging Biopolymer Networks, Biophysical Journal, 98(3), L1-L3, (2010)

W. Mickel*, S. Münster,* L.M. Jawerth, D.A. Vader, D.A. Weitz, A.P. Sheppard, K. Mecke, B. Fabry, G. Schroeder-Turk, Robust Pore Size Analysis of Filamentous Networks from Three-Dimensional Confocal Microscopy, Biophysical Journal, 95(12), 6072-80, (2008)