Understanding the influence of the biophysical environment on normal cell biology has been our central focus for some time. Many of the mechanical stimuli osteoblasts respond to, and the downstream signaling events that are initiated have been identified. What is still unknown, however, is the identity of a cell-bound mechanosensor or mechanosensory complex, which would initiate the conversion of a localized biophysical signal into an intracellular signaling response. We are investigating the role of annexins, calcium-dependent phospholipid-binding proteins, as a possible mechanosensors. We are also looking at the role of lipid rafts in mechanosignaling since annexins can localize to these membrane regions, which may be the initiation points of mechanosensing.