ABSTRACT

The development of the atomic force microscope (AFM) helped usher in the era of “nanotechnology” with its ability to measure (1) atomic interactions between molecules and (2) image components at the molecular level. In this chapter, we describe the use of the AFM to investigate novel treatment strategies for the autoimmune thrombotic condition known as the antiphospholipid (aPL) syndrome (APS). This coagulation-based disorder has been hypothesized to be caused by disruption of an anticoagulant two-dimensional

crystalline lattice of annexin V (AnxA5) present on the surface of placental trophoblasts and damaged endothelial cells. We present evidence supporting the premise that antibody-induced defects to this AnxA5 crystal shield may be “patched” through treatment with the synthetic antimalarial drug hydroxychloroquine, or with a phospholipid-binding phage-display heptapeptide. Critical to the outcome of the experiments was the ability to use high-resolution atomic force microscopy as a “nanoinstrument” to image reaction components in a non-ixed luid environment.