Deciphering mechanical signal processing at the interface between cell, basement membrane, and extracellular matrix
All cells in every tissue receive dynamic mechanical signals from their physiological niche and also generate such signals. Our work aims to understand the mechanobiological signaling cascades that regulate cell and tissue function. To recapitulate reciprocal signal processing between cells, basement membrane (BM), and extracellular matrix (ECM), we apply physiological mechanical ECM cues to biomimetic 3D cell cultures We use these versatile cell models, e.g. BM-covered breast spheroids, to study fundamental signaling circuits of cellular mechanoadaptation that orchestrate epithelial tissue development and neuronal network function.
We focus on the BM’s role as a physical cell migration barrier and signaling platform for reciprocal mechanotransduction of ECM stresses. Intriguingly, cells sense ECM stiffness by highly dynamic BM-penetrating protrusions and modulate thereby actomyosin-driven cell forces as consequence. We investigate the underlying signal processing circuits of mechanical BM disruption that lead to loss of tissue integrity.
ECM-transmitted shear strain is a fundamental but poorly understood mechanical cue steering cell differentiation. We develop unique cell culture devices to apply nature-like ECM-transmitted shear strain on developing breast gland spheroids. This approach enables to study cellular mechanoadaptation mechanisms in response to nature-like ECM signals.
Mechanobiology of Cell-BM-ECM interfaces, Mechanotransduction Mechanisms, Cellular and BM Invasion Mechanisms, Cell Network Formation, Cell and ECM Force Machinery
Dr. Erik Noetzel-Reiss
Building 02.4w / Room 338
1. Eschenbruch J, Dreissen G, Springer R, Konrad J, Merkel R, Hoffmann B and Noetzel E (2021). From Microspikes to Stress Fibers: Actin Remodeling in Breast Acini Drives Myosin II-Mediated Basement Membrane Invasion. Cells 10(8): 1979.
2. Gaiko-Shcherbak A, Eschenbruch J, Kronenberg NM, Teske M, Wolters B, Springer R, Gather MC, Merkel R, Hoffmann B and Noetzel E (2021). Cell Force-Driven Basement Membrane Disruption Fuels EGF- and Stiffness-Induced Invasive Cell Dissemination from Benign Breast Gland Acini. Int J Mol Sci. 22(8):3962.
3. Rose M, Noetzel E, Kistermann J, Eschenbruch J, Rushrush S, Gan L, Knüchel R, Gaisa NT, Dahl E (2021). The ECM Modulator ITIH5 Affects Cell Adhesion, Motility and Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder Cancer Cells. Cells. 10(5):1038.
4. Wiedenhoeft T, Braun T, Springer R, Teske M, Noetzel E, Merkel R, Csiszár A (2020). The basement membrane in a 3D breast acini model modulates delivery and anti-proliferative effects of liposomal anthracyclines. Pharmaceuticals. 13(9):1-17.
5. Fabris G, Lucantonio A, Hampe N, Noetzel E, Hoffmann B, DeSimone A Merkel R (2018). Nanoscale Topography and Poroelastic Properties of Model Tissue Breast Gland Basement Membranes. Biophys J. 115(9):1770-1782.
6. Schlensog M, Magnus L, Heide T, Eschenbruch J, Steib F, Tator M, Kloten V, Rose M, Noetzel E, Gaisa NT, Knüchel R, Dahl E. (2018). Epigenetic loss of putative tumor suppressor SFRP3 correlates with poor prognosis of lung adenocarcinoma patients. Epigenetics. 13(3):214-227.
7. Rose M, Kloten V, Noetzel E, Gola L, Ehling J, Heide T, Meurer SK, Gaiko-Shcherbak A, Sechi AS, Huth S, Weiskirchen R, Klaas O, Antonopoulos W, Lin Q, Wagner W, Veeck J, Gremse F, Steitz J, Knüchel R, Dahl E. (2017). ITIH5 mediates epigenetic reprogramming of breast cancer cells. Mol Cancer 16(1):44.
8. Gaiko-Shcherbak A, Fabris G, Dreissen G, Merkel R, Hoffmann B and Noetzel E (2015). The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini. PloS One 10(12):1-20.
9. Noetzel E, Rose M, Bornemann J, Gajewski M, Knüchel R, Dahl E. (2011). Nuclear transport receptor karyopherin-α2 promotes malignant breast cancer phenotypes in vitro. Oncogene 31:2101-2114
10. Noetzel E, Rose M, Sevinc E, Hilgers RD, Hartmann A, Naami A et al. (2010). Intermediate Filament Dynamics and Breast Cancer: Aberrant Promoter Methylation of the Synemin Gene Is Associated With Early Tumor Relapse. Oncogene 29:4814-4825.