Fig. 26. Elastic energy equilibrium: Focal point for vascular homeostasis.

During differentiation, each cell type establishes unique, evolutionally optimized cellular stresses that determine internal structure and responses to external stimuli. The stresses establish and define an optimized elastic energy setpoint or equilibrium (Section 5.). The elastic energy setpoint provides a governing framework for the way the twin sensory stimuli of cellular deformation and shear stress interact, thus coordinating mechanotransduction events that maintain homeostasis. (A) Vascular endothelial cells sense changes in their lumen volume by force-induced deformation of their shape; (B) the same cells sense flow changes by monitoring shear stress on their walls. The aqueous outflow system behavior illustrates how cell deformation and shear stress provide feedback loops in the vasculature that maintain volume and flow homeostasis. Increased pressure induces instantaneous increases in cellular deformation that act as a sensory signal. Cellular deformation or strain causes the cell membrane, cytoskeletal elements, organelles, nuclear membrane, nuclear intermediate filaments, and attached chromatin to all alter their configuration. Cell and tissue constituents respond to the signal by adjusting the tissue and cellular elastance. The altered elastance restores the elastic energy equilibrium that ensures appropriate tissue distension and recoil. Shear stress detects flow. With a constant volume flowing through a vessel, narrowing of the lumen increases flow, resulting in higher shear stress; the increase initiates responses in cells, contiguous extracellular matrix, and muscle in the vessel walls that lead to enlargement of the lumen. Lumen enlargement restores the lumen dimensions and linked shear stress to an equilibrium. Volume changes that induce cell wall deformation and shear responses work in unison to achieve the same homeostatic cell and vessel wall endpoint. From Johnstone Glaucoma Lab, University of Washington, Adapted from Johnstone M, The aqueous outflow system as a mechanical pump: J Glaucoma 13, 421–438.