AFM-Based Molecular Imaging and Nanomechanics of Extracellular Matrix

We are utilizing molecular scale atomic force microscopy, high resolution- and lateral force spectroscopy to investigate the nanoscale structure and mechanical properties of extracellular matrix molecules such as aggrecan, a critically important matrix constituent of cartilage, intervertebral discs, and other tissues subjected to compressive loading. AFM images of aggrecan provide detailed structural information, including the ultrastructure of the aggrecan core protein and the spatial distribution of long chain glycosaminoglycans attached to the core protein. These features cannot be assessed by conventional biochemical means. In collaboration with Professor Christine Ortiz (DMSE), we are studying age- and disease-related changes in human aggrecan structure and associated changes in nanoscale compressibility and lateral deformability. Such changes may be directly linked to known differences in the deformational behavior of human cartilage in health and disease, such as occurs in the in early stages of osteoarthritis. These studies are combined with state-of-the-art biochemical and molecular biological analyses of such extracellular matrix molecules. Recent discoveries include the finding that aggrecan synthesized by adult marrow-derived stromal cells resembles aggrecan from young growth cartilage, suggesting that BMSCs are promising candidates for cartilage tissue engineering.