Cell-cell meehanotransduction which involves sensing mechanical stimuli such as fluid induced shear stress and spreading the signal in the connected network of bone cells or among endothelial cells is still not well understood. Our studies here address several vital links that are overlooked by previous studies. Current knowledge on how these cells behave under fluid shear stress with possible candidates for mechanosensors are discussed in Chapter 1.

In Chapter 2, we first tested the hypothesis that fluid shear stress modifies expression, function and distribution of junctional proteins (Cx43, Cx45, and ZO-1) in cultured bone cells. Cell lines with osteoblastic (MC3T3-E1) and osteocytic (MLO-Y4) phenotypes were exposed to shear stress of 5 or 20 dyn/cm² for 1-3 h. Our results indicate that in cultured bone cells fluid shear stress disrupts junctional communication, rearranges junctional proteins and determines de novo synthesis of specific connexins to an extent that depends on the magnitude of the shear stress. Such disconnection from the bone cell network may provide part of the signal whereby the disconnected cells or the remaining network initiate focal bone remodeling.

In Chapter 3, we propose a new conceptual model for the cytoskeletal organization of endothelial cells (ECs) with a major dichotomy in structure and function at its basal and apical aspects. Intracellular distributions ofF-actin, vinculin, paxillin, ZO1 and Cx43 were analyzed following five hours of shear stress. Our results are explained in terms of a ‘bumper car’ model in which the actin cortical web (ACW) and dense peripheral actin band (DPAB) are only loosely connected to basal attachment sites allowing for two distinct cellular signaling pathways in response to fluid shear stress, one transmitted by glycocalyx core proteins as a torque that acts on the ACW and DPAB and the other emanating from focal adhesions and stress fibers (SFs) at the basal and apical membranes of the cell.

Chapter 4 recapitulates past and present key insights and proposes future directions.