Role of the plasma membrane in endothelial cell mechanosensation of shear stress

Mechanotransduction, which is the process by which cells convert mechanical stimuli to biochemical signaling cascades, is involved in the homeostasis of numerous tissues (reviewed in [21] and [56]). The mechanotransduction of hemodynamic shear stress by endothelial cells (ECs) has garnered special attention because of its role in regulating vascular health and disease. In particular, there is intense interest in identifying the primary molecular mechanisms of the EC sensing of shear stress because its (or their) discovery may lead to clinical interventions in atherosclerosis and other diseases related to mechanobiology. In this chapter, we address the hypothesis that the plasma membrane lipid bilayer is one endothelial cell mechanosensor. Here we define ’mechanosensor’ as a cellular structure that responds to mechanical stress and initiates mechanotransduction in response to shear stress without involving chemical second messengers. Mechanotransduction, then, is the process by which cells convert this sensory stimulus into changes in biochemical signaling. We define mechanobiology as the study of the entire process of sensation, transduction, and attendant changes in cell phenotype. Because mechanical linkages from the cell surface to lateral, internal, and basal parts of the cell redistribute forces imposed on the cell surface, many structures could serve as mechanosensors. Furthermore, mechanotransduction can involve direct force effects on molecules, diffusion- or convection-mediated transport of molecular second messengers, and the active transport of signaling molecules by molecular motors. Other chapters in this text will address other candidate mechanosensors (e.g., focal adhesions and their integrins). With respect to the membrane, in the context of these definitions, if shear stress induces a perturbation of the membrane constituents, and this perturbation is necessary for mechanotransduction, then the lipid bilayer is considered a mechanosensor. Similarly, if the shear stress acting on the apical portion of the cell leads to the perturbation of the membrane on the basal portion as a result of mechanical linkage, and this membrane perturbation is necessary for subsequent downstream signaling, then we consider the basal membrane also as a mechanosensor.