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Projekte im Verbundkolleg Gesundheit

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Investigating the role of integrin signaling in articular cartilage biomechanics by indentation type atomic force microscopy and single cell force spectroscopy

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

Verena Maier

Hochschule für angewandte Wissenschaften München

Koordination

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Dr. Sabine Fütterer-Akili

Dr. Sabine Fütterer-Akili

Koordinatorin BayWISS-Verbundkolleg Gesundheit und BayWISS-Verbundkolleg Economics and Business

Universität Regensburg
Zentrum zur Förderung des wissenschaftlichen Nachwuchses
Universitätsstraße 31
93053 Regensburg

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