An Integrative Review of Mechanotransduction in Endothelial, Epithelial (Renal) and Dendritic Cells (Osteocytes)

Abstract

In this review we will examine from a biomechanical and ultrastructural viewpoint how the cytoskeletal specialization of three basic cell types, endothelial cells (ECs), epithelial cells (renal tubule) and dendritic cells (osteocytes), enables the mechano-sensing of fluid flow in both their native in vivo environment and in culture, and the downstream signaling that is initiated at the molecular level in response to fluid flow. These cellular responses will be discussed in terms of basic mysteries and paradoxes encountered by each cell type. In ECs fluid shear stress (FSS) is nearly entirely attenuated by the endothelial glycocalyx that covers their apical membrane and yet FSS is communicated to both intracellular and junctional molecular components in activating a wide variety of signaling pathways. The same is true in proximal tubule (PT) cells where a dense brush border of microvilli covers the apical surface and the flow at the apical membrane is negligible. A four decade old unexplained mystery is the ability of PT epithelia to reliably reabsorb 60% of the flow entering the tubule regardless of the glomerular filtration rate. In the cortical collecting duct (CCD) the flow rates are so low that a special sensing apparatus, a primary cilia is needed to detect very small variations in tubular flow. In bone it has been a century old mystery as to how osteocytes embedded in a stiff mineralized tissue are able to sense miniscule whole tissue strains that are far smaller than the cellular level strains required to activate osteocytes in vitro.

PLS3 Mutations in X-Linked Osteoporosis with Fractures

“…[21][22][23] These dendrites are important for mechanosensing (converting mechanical signals into intracellular bio chemical signals to osteoblasts and osteoclasts). 24 The loss of sensor-cell mechanosensitivity has been proposed as a cause of osteoporosis. 25 We hypothesize that PLS3 mutations lead to decreased mechanosensing of osteocytes, with subsequent dysregulation of bone modeling or remodeling, which results in osteoporosis and fractures.…”

The glycocalyx and its significance in human medicine

“…Qazi et al [14] presented confocal images of HS for high metastatic kidney carcinoma cells (SN12L1) suspended in a 3D collagen I gel. The GCX thickness can be estimated from their Osteocytes are generally believed to be the mechanosensing cells in bone, and interstitial fluid flow shear stress induced by the cyclic compression of locomotion is widely believed to be the principal mechanical force applied to osteocytes, not the associated solid micro-strain [16]. Reilly et al [17], using the MLO-Y4 osteocytic cell line, demonstrated a GCX layer rich in HA.…”

Numerical analysis for elucidation of mechanical interaction between an erythrocyte moving in medium subject to inclined centrifugal force and endothelial cells on a plate

“…Especially, erythrocytes, or red blood cells, flow in blood capillaries interacting with the vascular endothelial surface layer. In general, it is believed that complex interactions occur between erythrocytes and the endothelial surface layer (ESL) (Weinbaum, et al, 2011). The ESL is also called endothelial glycocalyx layer (EGL), which consists of glycocalyx bushes, the height of which ranges from sub-micron order to a few-micron order (Gouverneur, et al, 2006).…”