The integrity of cohesive tissues strongly depends on the presence of the extracellular matrix, which provides support and anchorage for cells. The fibronectin protein and the heparin-like glycosaminoglycans are key components of this dynamic structural network. In this report, atomic force spectroscopy was used to gain insight into the compliance and the resistance of the fibronectin-heparin interaction. We found that this interaction can be described by an energetic barrier width of 3.1 +/- 0.2 angstrom and an off-rate of 0.2 +/- 0.1 s(-1). These dissociation parameters are similar to those of other carbohydrate-protein interactions and to off-rate values reported for more complex interactions between cells and extracellular matrix components. Our results indicate that the function of the fibronectin-heparin interaction is supported by its capacity to sustain significant deformations and considerable external mechanical forces. (C) 2007 Elsevier Inc. All rights reserved.