The most frequent musculoskeletal disease worldwide is osteoarthritis (OA), its prevalence is rising and a cure has not been found yet. Therefore, a more comprehensive understanding of the pathophysiology of articular cartilage and its cellular and molecular components remains in the focus of research. β1 integrins are essential receptors for chondrocyte-matrix interactions controlling the structural organization and biomechanical properties of cartilaginous tissues, which are required to maintain normal articular cartilage function. For example, the collagen-binding α10-β1 integrin contributes to cartilage morphogenesis and is required for efficient chondrogenesis of mesenchymal stem cells (MSC). The role of collagen-binding integrins in articular cartilage function and chondrocyte mechano-transduction is to be further elaborated in this doctoral thesis.
The major goal is to dissect the contribution of individual collagen-interacting integrins to the development of OA and to the response of β1 integrins to cytokine and mechanical stimulation. Furthermore, the effect of overexpression of the gene encoding α10 integrin will be investigated. Atomic force microscopy (AFM) will be used to perform stiffness measurements in order to quantify the mechanical properties of selected samples. Additionally, AFM-based single-cell force spectroscopy will be applied to explore cell-cell and cell-substrate interactions to elucidate the effect of lack of collagen-interacting integrins on the collagen-binding capacity of chondrocytes. The results of these experiments are expected to deliver a more comprehensive understanding of joint tissue pathophysiology, to help identify and verify novel targets for diagnosis and therapeutic intervention, and, eventually, to assist in the development of novel strategies to halt OA progression.
Verena Maier
Investigating the role of integrin signaling in articular cartilage biomechanics by indentation type atomic force microscopy and single cell force spectroscopy
MEMBER IN THE JOINT ACADEMIC PARTNERSHIP
since
Joint Academic Partnership Health
Supervisor Hochschule München University of Applied Sciences:
Prof. Dr. Hauke Clausen-Schaumann
Projects:
- Investigating the role of integrin signaling in articular cartilage biomechanics by indentation type atomic force microscopy and single cell force spectroscopy
- Mechanische Charakterisierung von biologischen Materialien mittels der Laser-Doppler Vibrometrie
- Investigation of structure function relationships in degraded articular cartilage using indentation-type atomic force microscopy and novel strategies to determinethe degradation depth.
- Strukturelle und biomechanische Analyse des Gelenkknorpels von genetischen Mausmodellen mittels Rasterkraftmikroskopie
- Mechanotransduction on the single cell level
- Laser-induced transfer of human mesenchymal cells using near infrared femtosecond laser pulses for the precise configuration of cell nichoids
- Herstellung eines 3D Gewebemodells zur Untersuchung und gezielten Stimulation von Zellmigration und Zellwachstum entlang von E-Modul Gradienten der Extrazellulären Matrix
- Entwicklung einer 3D-gedruckten Mikrofluidik zur Analyse der Fluiddynamik in Blutgefäßen
