Chemical and Mechanical Micro-Diversity of the Extracellular Matrix

Interaction with the extracellular matrix (ECM) triggers multiple physiological responses in living cells, affecting their structure, function and fate. Recent studies have demonstrated that cells can sense a wide variety of chemical and physical features of the ECM, and differentially respond to them. Thus, cells cultured on flat surfaces coated with two different integrin-reactive adhesive proteins, fibronectin and vitronectin, display varying degrees of spreading on these matrices, and form morphologically distinct types of matrix adhesions, with variable prominence and spatial distribution of both focal and fibrillar adhesions. It was further shown, using labeling with different antibodies which bind to distinct sites on the fibronectin molecule, that even a “molecularly homogeneous” matrix displays spatial micro-heterogeneity, exposing distinct epitopes at different locations. Diversification of the adhesive surface can be induced by the application of mechanical force to the elastic fibronectin matrix, resulting in the formation of different patterns of fibrillar ECM arrays. Time-lapse monitoring of matrix fibrillogenesis by cells expressing fluorescently tagged fibronectin demonstrated that the assembly of fibrils in such cell cultures occurs when the leading lamella of the cell advances, attaches to the substrate-bound fibronectin, and then retracts backwards, thus applying tensile forces to the attached fibronectin. These results indicate that the ECM is a highly complex cellular environment, whose chemical and physical properties are directly regulated by the attached cells.