Proteoglycan aggregate is a major component of the extracellular matrix in articular cartilage and is considered to be responsible for the resistance to compression of this tissue. The reduced stiffness of articular cartilage due to the loss of proteoglycan aggregate has been reported in osteoarthritis. In order to understand the mechanical properties of extracellular matrix in articular cartilage at molecular level, the compressive properties of 36 single molecules of proteoglycan aggregate were directly measured using a laser tweezers/interferometer system. The proteoglycan aggregates showed resistance when compressed to similar to30% of their contour length. The stiffness of proteoglycan aggregates increased non-linearly from 2.6 +/- 3.8 pN/mum (compressed to 30-35% of their contour length) to 115.5 +/- 30.9 pN/mum (compressed to 2.5-5% of their contour length). (C) 2004 Elsevier Inc. All rights reserved.