Abstract
The endothelial glycocalyx (eGlx) is thought to be the primary macromolecular filter for fluid flux out of the vasculature. This filter maintains the higher protein concentration within the vessel lumen relative to the tissue. Whilst the arguments for the eGlx being the size filter are convincing the structural evidence has been limited to specialized stains of perfusion fixed tissue, which are further processed for resin embedding for transmission electron microscopy. The staining and processing of the delicate pore structure has left many researchers struggling to interpret the observed surface coat. Previous work has alluded to a 19.5 nm spacing between fibers; however, whilst repeatable it does not give an eGlx pore size consistent with known glycosaminoglycan (GAG) molecular structure due to the required fiber thickness of >10 nm. Here a new interpretation is proposed based on the likelihood that the electron micrographs of are often of collapsed eGlx. The 19.5 nm spacing measured may therefore be the core protein of the proteoglycans (PGs) with the GAGs wrapped up around them rather than in an expanded in vivo state. The concept is explored to determine that this is indeed consistent with experimental measurements of permeability if the syndecans are predominately dimerized. Further an alteration of core protein lattice from hexagonal packing to square packing dramatically changes the permeability which could be facilitated via known mechanisms such as transient actin binding.
Highlights
For most capillaries the primary method of fluid exchange between the plasma and the tissues is defined by the Starling Hypothesis as interpreted in 1997 by CC Michel (1997) and Weinbaum (1998) often dubbed the “revised Starling hypothesis.” With this interpretation, in the steady state, the oncotic pressure ( ) difference resisting the hydrostatic pressure (P) is across the endothelial glycocalyx rather than the whole vessel wall: Jv = LpA [(Plumen − PeGlx) − σ] (1)Where the Jv is the volumetric fluid flux, Lp the hydraulic conductivity and A the capillary surface area
Where ∅ is the partition coefficient defined as the relative free space between the solute (Fs) and the water (Fw): Fs ∅=
Regardless, clearly the stains are affecting the structure, and adding to the size of the GAGs when bound
Summary
The different hydraulic conductivities across tissues are of physiological importance, and allow normal processes such as an immune response to manipulate the molecular size ratio of transported molecules (Owen-Woods et al, 2020) Until this point the remaining unknown was to confirm the pore size of the eGlx. A study of electron micrographs and a limited number of Pt/C replicate micrographs from freezeetched frog mesenteric and pulmonary vessels indicated a spacing between the eGlx fibers of 19.5 nm (Squire et al, 2001). There is an issue between linking the ≈20 nm spacing repeatedly observed in perfusion fixed resin embedded electron microscopy and the expected 7–8 nm pore size to exclude albumin, as the required fiber thickness would be too large to fit with our understanding of eGlx composition. There are a multitude of unknowns and as such the subsequent interpretation of the electron microscopy is not claimed as definitive, but instead claims to fit current understanding consistently and offers a promising alternative on previous interpretations
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