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Matrix Elasticity

Are endothelial cells responding to changes in the matrix elasticity? Our previous studies show, that upon shear stress stimulation, endothelial cells (EC) actively release the growth factor FGF-2. This release of FGF-2 is initiated by protease activation, a process that is further controlled by specific cell matrix adhesion. In general, proteolytic digestion of the extracellular matrix change its stiffness and by that might have profound effects on cell matrix interactions.

Summarizing our phenomenological observations so far, it is attractive and reliable to assume that cell-matrix-interaction are critically involved in the initiation and maintenance signaling cascades supporting a proper vascular wall function. However, knowledge of the exact molecular mechanisms underlying these processes is incomplete and it is not clear how such matrix modifications are established and whether they have influence on EC phenotype.

We try to address that question, drawing the hypothesis that, similar to stem cells, the phenotype of EC might be dependent on the elastic properties of the extracellular matrix (e.g. the vascular wall). We pay special interest on cellular phenotypes and signaling responses induced by changes in the matrix stiffness. Since during vascular remodeling processes, matrix proteases are often activated and seem to be critically involved in generation and maintenance of signaling cascades in adaptive vascular remodeling, we propose that due to those proteolytic activities the matrix stiffness is altered and influences EC phenotype.

We further hypothesize that beside specific cell-matrix interactions also the matrix elasticity might bear stimuli guiding endothelial cells to appropriate adaptive remodeling of the vessel wall. Indeed, first experiments could show that fragmentation of matrix proteins changes the local microarchitecture and exhibit modulator properties for adhesion dependent signaling. Moreover, EC grown on soft matrices tend to go into apoptosis. Cells grown on intermediate flexible matrices are intending to form new capillary-like structures, and, finally, cells on stiff matrices are highly proliferative. This in vitro culture regime might serve as a model system to study not only development and progression of vascular remodeling but also of arteriosclerosis and high blood pressure.