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Cell maturation and differentiation

Living cells are embedded in a defined environment, characterized by the specific mechanical properties topography, elasticity and strain. As example, elasticities of glandular tissue (very soft) highly differ from cartilage tissue (stiff) and nerve cells. The latter are typically barely affected by strain while endothelial cells forming the inner layer of arteries become cyclically strained by up to 20% with every heart beat. Such specific mechanical environmental conditions are recognized most likely by every adhesive cell type via mechanosensoric mechanisms to be transformed into specific cellular responses. These include small, short term adaptations as well as highly complex mechanisms as cell maturation or cell differentiation. Various important publications have shown the ability to direct differentiation into neurogenic (nerve cells), myogenic (muscles) and osteogenic (cartilage and bone) direction in an exclusively substrate elasticity dependent manner for embryonic stem cells (Engler et al. 2006, Cell). Among analyzing the differentiation potential of adult mesenchymal stem cells (MSCs) we concentrate on the role of mechanical signals, especially substrate elasticity, for maturation and differentiation processes of muscular cell systems as well as for the differentiation of cardiac fibroblasts to myofibroblasts. Such experiments allow us to mimic nature-like-conditions on cell culture levels to characterize in detail mechano-functional alterations and adaptations of e.g. heart muscle cells or cardiac fibroblasts known to occur naturally in mammals upon aging or after diseases (e.g. heart attack).

DifferenzierungCardiac fibroblasts (left) differentiate to myofibroblasts (right) in an elasticity dependent manner (1 kPa to 130 kPa). As result, actin cytoskeleton (green) as well as adhesion structures (red) are intensively remodelled and modified in protein composition leading to massive changes in mechanical properties of both cell types.

To generate nature-like substrate elasticities for cell culture we use tunable silicone rubber systems. Using those systems we circumvent strongly artificial elasticity conditions commonly occurring in classical cell culture systems with elasticities approximately 1,000,000 times stiffer than mammalian tissues.

For further questions please contact: Dr. Bernd Hoffmann