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We study the interactions between cells and extracellular substrates. As the knowledge about the complexity of the extracellular matrix and the number of corresponding receptors on the cell surface has grown considerably in recent years, the significance of the influence of extracellular substrates on cell behavior has been increasingly acknowledged. We are interested in screening whole panels of substrates to (i) compare the strength and specificity of the binding of cells to extracellular substrates and (ii) compare the cellular responses after cell binding to different substrates. For example, we study adhesion properties of cells derived from tumors to investigate correlations between cell adhesion profiles and metastasis. Another study focuses on the regeneration of articular cartilage defects. In this study, we characterize adhesion profiles of primary chondrocytes from patients with knee osteoarthritis. We hope that through the control of cell-matrix interactions, we will be able to stabilize chondrocyte phenotype and support the regeneration of osteoarthritic cartilage lesions. In the future, we will aim at screening cell-substrate interactions for systems biology to determine how signals generated from such interactions affect the intracellular regulatory network that determines cell function and differentiation.
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We report the development of a protein microarray (MSA™) that allows for screening of multiple cell-substrate interactions on a miniaturized scale. The microarray consists of microspots of a panel of substrates (e.g., extracellular matrix proteins, peptides, or synthetic molecules) that are immobilized on a coated microslide surface. Cells are incubated on these arrays in mounted chambers and subsequently analyzed for cell adhesion or phenotype. Major advantages of our approach, compared to conventional assays in microplates, include the greatly reduced amounts of valuable reagents and cells and the ability to process many samples in parallel. This is particularly useful when only small amounts of cells are available (e.g., stem cells or other primary cells, such as cells from diseased tissues). The system was statistically evaluated to define the accuracy of quantitative analysis of differential cell adhesion. It is currently applied in various projects, including the profiling of cell adhesion of various tumor cell lines and chondrocytes in different pathological states.
Cell adhesion profiling using extracellular matrix protein microarrays, p. 523.
