The role of vinculin in coordinating cellular morphodynamics, force generation and ECM remodeling during cell migration in 2D and 3D environments Coordinated cell migration is critical for tissue morphogenesis and homeostasis, and requires the integration of actin cytoskeleton based force generation and cell adhesion to the extracellular matrix (ECM) through integrin adhesion receptors. How force generation and ECM-adhesion affect cell motility has mainly been studied using two-dimensional (2D) cell culture substrates, which cannot recapitulate the mechanics of cell migration in vivo, where cells have to overcome the steric hindrance of the ECM to move forward. Three-dimensional (3D) matrices of collagen, fibrin, or cell-derived matrices are being used more frequently. However, how traction force generation, ECM-adhesion and physical parameters of the ECM influence cell migration in 3D environments still remains unclear, and can vary fundamentally between different cell types. The coordinated migration of cells in vivo is often associated with a remodeling of the ECM, which modulates haptic and mechanical guidance cues for the cells. In turn, excessive ECM-remodeling may promote cell motility in pathological conditions such as cancer metastasis. Cell motion and ECM-remodeling both depend on cellular traction forces, allowing cells to move forward and apply tension to remodel the ECM, suggesting a role for ECM-traction force generation in coordinating cell motion and ECM-remodeling. It remains unknown, however, which cytoskeleton and adhesion proteins are required to coordinate the remodeling of complex 3D matrices. The adhesion protein vinculin is present in cell-cell junctions and in focal adhesions (FA), where it links filamentous (F-) actin to the integrin-binding protein talin to transmit forces between actin cytoskeleton and ECM. Vinculin reduces cell migration on 2D substrates. In addition, vinculin expression is reduced in a number of human tumors, and cancer cells overexpressing vinculin show reduced metastatic capacity when injected into nude mice, suggesting that vinculin may also inhibit cell migration in vivo. However, vinculin seems to affect 3D cell migration fundamentally different from 2D cell migration, as it promotes the invasion of fibroblasts into 3D collagen gels. It remains unclear though, how vinculin facilitates cell invasion into collagen. The collagen invasiveness of different cancer cells correlated with the strain energy amounts generated by the cells, with the strain energy field anisotropy, and cell shape anisotropy . Vinculin affects both cell morphology and force generation on 2D substrates, suggesting that vinculin may also promote collagen invasion by modulating force generation and cell shape. It is not known, however, how vinculin affects cell morphodynamics, traction force generation, or ECM remodeling in complex 3D environments. We characterize the effects of vinculin gene disruption on cell migration, morphodynamics, force generation and ECM-remodeling of primary murine embryonic fibroblast (MEF) on 2D substrates and in 3D collagen I culture.

Dr. rer. nat.,summa cum laude, 10/2002 - 04/2007. Mouse Genetics/Cell Biology. Max-Planck-Institute of Biochemistry, Martinsried/Heinrich-Heine-University Duesseldorf, Germany. Prof. Dr. med. Reinhard Faessler Dipl. Biol., 10/1996 - 04/2002. Cell Biology/Biochemistry/Physics. Heinrich-Heine-University Duesseldorf, Germany. Prof. Dr. rer. nat. Wolfgang Schulz

Scientific Assistant, 03/2012 - present. Friedrich-Alexander University Erlangen-Nuremberg, Chair for Biophysics, Biophysics Group. Prof. Dr. Ben Fabry. Project: The role of vinculin in morphodynamics and force generation of primary murine embryonic fibroblasts and endothelial cells in 3D collagen matrices and in vivo Postdoctoral Fellow, 09/2007 - 02/2012. National, Heart, Lung and Blood Institute/National Institutes of Health, Cell Biology and Physiology Center, Laboratory of Cell and Tissue Morphodynamics. Prof. Dr. Clare M. Waterman, Ph.D.. Project: The role of vinculin in actin based force generation by focal adhesions in migrating primary murine embryonic fibroblasts Postdoctoral Fellow, 05/2007 - 08/2007. The Scripps Research Institute, Department of Cell Biology, Cell Motility Group. Prof. Dr. Clare M. Waterman, Ph.D.. Project: The role of vinculin in actin based force generation by focal adhesions in migrating primary murine embryonic fibroblasts Doctoral Student, 10/2002 - 04/2007. Department of Molecular Medicine, Max-Planck-Institute of Biochemistry, Martinsried. Prof. Dr. med. Reinhard Faessler. Project: Functional analysis of focal adhesion proteins of the parvin family by knockout in the mouse Diploma Student, 03/2001 - 03/2002. Research Laboratory of the Urological Clinic, Heinrich-Heine-University Duesseldorf. Prof. Dr. rer. nat. Wolfgang A. Schulz. Project: Basic and inducible activities of the Wnt- and Hedgehog-signaltransduction pathways in normal and transformed uroepithelial cells Undergraduate Student, 03/2000 - 12/2000. Department of Cell Biology, Institute of Zoomorphology, Cell Biology and Parasitology, Heinrich-Heine-University Duesseldorf. Prof. Dr. rer. nat. Jochen D´Haese. Project: Identification of flea populations by sequence analysis of the internal ribosomal spacer region 1

Course Assistant “Biomedical Imaging”, Department of Physics, Biophysics Group, Friedrich-Alexander University Erlangen-Nuermberg. 2014 Course Assistant “Experimental Physics”, Department of Physics, Biophysics Group, Friedrich-Alexander-University Erlangen-Nuremberg. 2012/2013 Teaching Assistant “Physiology Course”, Marine Biological Laboratory, Woods Hole. 2011 Teaching Assistant “Optical Microscopy and Imaging in the Biomedical Sciences”, Marine Biological Laboratory, Woods Hole. 2007 Course Assistant “Animal Morphology”, Institute of Zoomorphology, Cell Biology and Parasitology, Heinrich-Heine-University Duesseldorf. 2000

Projektleiter nach GenTSV, Friedrich-Alexander University Erlangen-Nuermberg, Chair for Physical and Medical Technology. 2013 Attendance at laboratory safety/operational courses, Projektleiter nach GenTSV, Sondermuell, Brandgefahren. 2013 National Heart, Lung and Blood Institute Fellows Advisory Committee Member, National Heart, Lung and Blood Institute/National Institutes of Health, Bethesda. 2010-2012 American Society for Cell Biology Member, since 2007

Travel Grant, 53^rd Annual Meeting of the American Society for Cell Biology, New Orleans, 2013 Travel Grant, Swedish Association for Cytoskeleton Research meeting “The Cytoskeleton in Development and Pathology”, Federation of the Societies of Biochemistry and Molecular Biology (FEBS)”. 2010 Fellows Award for Research Excellence 2010, National Institutes of Health, Bethesda. 2009

2025

Contractility of striated muscle tissue increases with environmental stiffness according to a power-law relationship

Kah, Delf; Lell, Julia; Wach, Tina; Spörrer, Marina; Dessalles, Claire A.; Kraxner, Julia; Wiedenmann, Sandra; Gerum, Richard C.; Vergarajauregui, Silvia; Esser, Tilman U.; Böhringer, David; Engel, Felix B.; Thievessen, Ingo; Fabry, Ben

npj Biological Physics and Mechanics (2025)

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2023

Long-term stability of aerophilic metallic surfaces underwater

Tesler, A. B.; Kolle, S.; Prado, L. H.; Thievessen, I.; Bohringer, D.; Backholm, M.; Karunakaran, B.; Nurmi, H. A.; Latikka, M.; Fischer, L.; Stafslien, S.; Cenev, Z. M.; Timonen, J. V. I.; Bruns, M.; Mazare, A.; Lohbauer, U.; Virtanen, S.; Fabry, B.; Schmuki, P.; Ras, R. H. A.; Aizenberg, J.; Goldmann, W. H.

Nat Mater (2023)

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2022

Calcium supplementation of bioinks reduces shear stress-induced cell damage during bioprinting

Fischer, Lena; Nosratlo, Mojtaba; Hast, Katharina; Karakaya, Emine; Ströhlein, Nadine; Esser, Tilman U.; Gerum, Richard; Richter, Sebastian; Engel, Felix; Detsch, Rainer; Fabry, Ben; Thievessen, Ingo

Biofabrication (2022)

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A New Printable Alginate/Hyaluronic Acid/Gelatin Hydrogel Suitable for Biofabrication of In Vitro and In Vivo Metastatic Melanoma Models

Schmid, R.; Schmidt, S. K.; Detsch, R.; Horder, H.; Blunk, T.; Schrufer, S.; Schubert, D. W.; Fischer, L.; Thievessen, I.; Heltmann-Meyer, S.; Steiner, D.; Schneidereit, D.; Friedrich, O.; Gruneboom, A.; Amouei, H.; Wajant, H.; Horch, R. E.; Bosserhoff, A. K.; Arkudas, A.; Kengelbach-Weigand, A.

Advanced Functional Materials (2022)

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Role of Fiber Thickness and Surface Treatment of Electrospun Polycaprolactone Matrices on the Growth of Different Breast Cancer-Associated Cells

Sivakumar, Sankaranarayanan; Schmid, Rafael; Wieland, Annalena; Strissel, Pamela L.; Strick, Reiner; Fischer, Lena; Thievessen, Ingo; Kataev, Elmar; Arkudas, Andreas; Horch, Raymund E.; Schubert, Dirk W.; Kengelbach-Weigand, Annika

Advanced Materials Interfaces (2022)

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The desmin mutation R349P increases contractility and fragility of stem cell-generated muscle micro-tissues

Spörrer, Marina; Kah, Delf; Gerum, Richard C.; Reischl, Barbara; Huraskin, Danyil; Dessalles, Claire A.; Schneider, Werner; Goldmann, Wolfgang H.; Herrmann, Harald; Thievessen, Ingo; Clemen, Christoph S.; Friedrich, Oliver; Hashemolhosseini, Said; Schröder, Rolf; Fabry, Ben

Neuropathology and Applied Neurobiology (2022)

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Nontoxic Liquid-Infused Slippery Coating Prepared on Steel Substrates Inhibits Corrosion and Biofouling Adhesion

Tesler, Alexander B.; Prado, Lucia H.; Thievessen, Ingo; Mazare, Anca; Schmuki, Patrik; Virtanen, Sannakaisa; Goldmann, Wolfgang H.

ACS Applied Materials & Interfaces (2022)

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The focal adhesion protein β-parvin controls cardiomyocyte shape and sarcomere assembly in response to mechanical load

Thievessen, Ingo; Suhr, Frank; Vergarajauregui, Silvia; Böttcher, Ralph T.; Brixius, Klara; Rosenberger, Georg; Dewald, Oliver; Fleischmann, Bernd K.; Ghanem, Alexander; Krüger, Marcus; Engel, Felix B.; Fabry, Ben; Bloch, Wilhelm; Fässler, Reinhard

Current Biology (2022)

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2021

Functional genomics meta-analysis to identify gene set enrichment networks in cardiac hypertrophy

Angeloni, M.; Thievessen, I.; Engel, F. B.; Magni, P.; Ferrazzi, F.

Biol Chem (2021)

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pyTFM: A tool for traction force and monolayer stress microscopy

Bauer, Andreas; Prechová, Magdalena; Fischer, Lena; Thievessen, Ingo; Gregor, Martin; Fabry, Ben

PLOS Computational Biology (2021)

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From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking

Hahn, L.; Beudert, M.; Gutmann, M.; Kessler, L.; Stahlhut, P.; Fischer, L.; Karakaya, E.; Lorson, T.; Thievessen, I.; Detsch, R.; Luhmann, T.; Luxenhofer, R.

Macromol Biosci (2021)

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Molecular Changes Induced in Melanoma by Cell Culturing in 3D Alginate Hydrogels

Kappelmann-Fenzl, Melanie; Schmidt, Sonja K.; Fischer, Stefan; Schmid, Rafael; Lämmerhirt, Lisa; Fischer, Lena; Schrüfer, Stefan; Thievessen, Ingo; Schubert, Dirk W.; Matthies, Alexander; Detsch, Rainer; Boccaccini, Aldo R.; Arkudas, Andreas; Kengelbach-Weigand, Annika; Bosserhoff, Anja K.

Cancers (2021)

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PCL micro-dumbbells – A new class of polymeric particles reveals morphological biofunctionality

Sonnleitner, David; Schäfer, Natascha; Wieland, Annalena; Fischer, Lena; Pasberg, Patrick; Thievessen, Ingo; Lang, Gregor

Applied Materials Today (2021)

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A One‐Pot Universal Approach to Fabricate Lubricant‐Infused Slippery Surfaces on Solid Substrates

Tesler, Alexander B.; Prado, Lucia H.; Khusniyarov, Marat M.; Thievessen, Ingo; Mazare, Anca; Fischer, Lena; Virtanen, Sannakaisa; Goldmann, Wolfgang H.; Schmuki, Patrik

Advanced Functional Materials (2021)

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2020

Strategies to evaluate alginate based bioinks applying extrusion printing for biofabrication

Karakya, Emine; Fischer, Lena; Hazur, Jonas; Boccaccini, Aldo R; Thievessen, Ingo; Detsch, Rainer

Transactions on Additive Manufacturing Meets Medicine (2020)

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AKAP6 orchestrates the nuclear envelope microtubule-organizing center by linking golgi and nucleus via AKAP9

Vergarajauregui, Silvia; Becker, Robert; Steffen, Ulrike; Sharkova, Maria; Esser, Tilman; Petzold, Jana; Billing, Florian; Kapiloff, Michael S.; Schett, George; Thievessen, Ingo; Engel, Felix B.

eLife (2020)

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2019

Treatment of keratinocytes with 4-phenylbutyrate in epidermolysis bullosa: Lessons for therapies in keratin disorders

Sporrer, Marina; Prochnicki, Ania; Tölle, Regine C.; Nyström, Alexander; Esser, Philipp R.; Homberg, Melanie; Athanasiou, Ioannis; Zingkou, Eleni; Schilling, Achim; Gerum, Richard; Thievessen, Ingo; Winter, Lilli; Bruckner-Tuderman, Leena; Fabry, Ben; Magin, Thomas M.; Dengjel, Jörn; Schröder, Rolf; Kiritsi, Dimitra

EBioMedicine (2019)

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2018

Vinculin regulates lamellipodium protrusion velocity.

Borau, C.; Aznar, J. M. G. a. r. c. i. a.; Fabry, B.; Thievessen, I.

(2018)

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β-parvin orchestrates the induction of physiological cardiac hypertrophy.

Thievessen, I.; Suhr, F.; Boettcher, R. T.; Fabry, B.; Bloch, W.; Faessler, R.

(2018)

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2016

Three-dimensional force microscopy of cells in biopolymer networks

Steinwachs, J.; Metzner, C.; Skodzek, K.; Lang, N.; Thievessen, I.; Mark, C.; Munster, S.; Aifantis, K. E.; Fabry, B.

Nat Methods (2016)

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2015

Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen

Thievessen, I.; Fakhri, N.; Steinwachs, J.; Kraus, V.; McIsaac, R. S.; Gao, L.; Chen, B. C.; Baird, M. A.; Davidson, M. W.; Betzig, E.; Oldenbourg, R.; Waterman, C. M.; Fabry, B.

FASEB J (2015)

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Vinculin F-actin interaction regulates lamellipodium protrusion velocity

Thievessen, I.; Borau, C.; Aznar, J. M. G. a. r. c. i. a.; Fabry, B.

(2015)

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2013

Vinculin, cell mechanics and tumour cell invasion

Goldmann, W. H.; Auernheimer, V.; Thievessen, I.; Fabry, B.

Cell Biol Int (2013)

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Vinculin-actin interaction couples actin retrograde flow to focal adhesions, but is dispensable for focal adhesion growth

Thievessen, I.; Thompson, P. M.; Berlemont, S.; Plevock, K. M.; Plotnikov, S. V.; Zemljic-Harpf, A.; Ross, R. S.; Davidson, M. W.; Danuser, G.; Campbell, S. L.; Waterman, C. M.

J Cell Biol (2013)

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2009

Cardiac Fibroblasts Require Focal Adhesion Kinase for Normal Proliferation and Migration

Manso, A. M.; Kang, S. M.; Plotnikov, S. V.; Thievessen, I.; Oh, J.; Beggs, H. E.; Ross, R. S.

Am J Physiol Heart Circ Physiol (2009)

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2008

SILAC Mouse for Quantitative Proteomics Uncovers Kindlin-3 as an Essential Factor for Red Blood Cell Function

Krüger, Marcus; Moser, Markus; Ussar, Siegfried; Thievessen, Ingo; Luber, Christian A.; Forner, Francesca; Schmidt, Sarah; Zanivan, Sara; Fässler, Reinhard; Mann, Matthias

Cell (2008)

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2006

γ-Parvin Is Dispensable for Hematopoiesis, Leukocyte Trafficking, and T-Cell-Dependent Antibody Response

Chu, Haiyan; Thievessen, Ingo; Sixt, Michael; Lämmermann, Tim; Waisman, Ari; Braun, Attila; Noegel, Angelika A.; Fässler, Reinhard

Molecular and Cellular Biology (2006)

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2005

Hedgehog signaling in normal urothelial cells and in urothelial carcinoma cell lines

Thievessen, Ingo; Wolter, Marietta; Prior, Andrea; Seifert, Hans-Helge; Schulz, Wolfgang A.

Journal of Cellular Physiology (2005)

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2004

Integrin-linked kinase: integrin's mysterious partner

Grashoff, C.; Thievessen, I.; Lorenz, K.; Ussar, S.; Fassler, R.

Curr Opin Cell Biol (2004)

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2003

Activities of MAP-Kinase Pathways in Normal Uroepithelial Cells and Urothelial Carcinoma Cell Lines

Swiatkowski, Sandra; Seifert, Hans-Helge; Steinhoff, Christine; Prior, Andrea; Thievessen, Ingo; Schliess, Freimut; Schulz, Wolfgang A.

Experimental Cell Research (2003)

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