Abstract
BackgroundRegulation of integrin binding to the specific complementary sites on extra-cellular matrix (ECM) proteins plays a major role in cell adhesion and migration. In addition to regulating single integrin-ligand bonds by affinity modulation, cells regulate their adhesiveness by forming integrin clusters. Although it is clear that cells exhibit different adhesion and migration behaviors on surfaces coated with different concentrations of ECM proteins, it is not clear if this response is mediated by changes in the availability of integrin binding sites or by differential intracellular signaling that may affect integrin binding and clustering.ResultsTo quantify how the concentration of ECM affects integrin clustering, we seeded cells expressing the integrin αIIbβ3 on different concentrations of the complementary ECM protein fibrinogen (Fg) and measured the resulting integrin cluster properties. We observed heterogeneity in the properties of integrin clusters, and to characterize this population heterogeneity we use a probabilistic modeling approach to quantify changes to the distributions of integrin cluster size, shape, and location.ConclusionsOur results indicate that in response to increasing ECM density cells form smaller integrin clusters that are less elongated and closer to the cell periphery. These results suggest that cells can sense the availability of ECM binding sites and consequently regulate integrin clustering as a function of ECM density.
Highlights
Regulation of integrin binding to the specific complementary sites on extra-cellular matrix (ECM) proteins plays a major role in cell adhesion and migration
Quantification of Integrin Cluster Properties To investigate the effect of ECM density on integrin clustering, we used immunofluorescence microscopy to visualize integrin clusters in Chinese Hamster Ovary (CHO) cells adhering to coverslips coated in different concentrations of Fg
CHO cells stably expressing aIIbb3 adhered and spread to Fg-coated coverslips, but not to those coated with Bovine Serum Albumin (BSA), confirming that cell adhesion depends upon a specific interaction of aIIbb3 with Fg
Summary
Regulation of integrin binding to the specific complementary sites on extra-cellular matrix (ECM) proteins plays a major role in cell adhesion and migration. It is clear that cells exhibit different adhesion and migration behaviors on surfaces coated with different concentrations of ECM proteins, it is not clear if this response is mediated by changes in the availability of integrin binding sites or by differential intracellular signaling that may affect integrin binding and clustering. Many types of integrins form micron-sized clusters, which create the foundation for various cell-matrix adhesion complexes including focal adhesions. These complexes are populated by a diverse group of membrane, structural, adaptor, and enzymatic proteins [1], and signaling via these complexes affects many important cellular processes [2]. Cells exhibit a phenomenon known as haptotaxis, or cell migration in response to a concentration gradient of adhesion ligand [17,18], a behavior that clearly requires the ability to direct cell migration in response to changes in ECM density
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