LB926 Hyaluronic acids (HAs) molecular size-dependent biological functions on UVB-induced DAMPs-mediated keratinocyte inflammation

Levan is a fructan-type exopolysaccharide which is produced by many microbes from sucrose via extracellular levansucrases. The hydrocolloid properties of levan depend on its molecular weight, while it is unknown why and to what extent levan is functionally diverse depending on its size. The aim of our study was to gain deeper insight into the size-dependent functional variability of levan. For this purpose, levans of different sizes were produced using the water kefir isolate Gluconobacter albidus TMW 2.1191 and subsequently rheologically characterized. Three levan types could be identified, which are similarly branched, but differ significantly in their molecular size and rheological properties. The smallest levan (<107 Da), produced without adjustment of the pH, exhibited Newton-like flow behavior up to a specific concentration of 25% (w/v). By contrast, larger levans (>108 Da) produced at pH ≥ 4.5 were shear-thinning, and the levan produced at pH 5.0 showed a gel-like behavior at 5% (w/v). A third (intermediate) levan variant was obtained through production in buffers at pH 4.0 and exhibited the properties of a viscoelastic fluid up to concentrations of 15% (w/v). Our study reveals that the rheological properties of levan are determined by its size and polydispersity, rather than by the amount of levan used or the structural composition.

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Blood-cerebrospinal fluid (CSF) barrier dysfunction means reduced CSF flow not barrier leakage - conclusions from CSF protein data

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x-anp-2020-0094 ◽

2021 ◽

Vol 79 (1) ◽

pp. 56-67

Author(s):

Hansotto REIBER

Keyword(s):

Cerebrospinal Fluid ◽

Flow Rate ◽

Serum Proteins ◽

Molecular Size ◽

Interindividual Variation ◽

Csf Flow ◽

Barrier Dysfunction ◽

Size Dependent ◽

Local Accumulation ◽

Experimental Allergic

ABSTRACT Background: Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such as barrier leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced CSF flow rate as the cause. Results: Even the severest barrier dysfunctions do not change the molecular size-dependent selectivity or the interindividual variation of the protein transfer across barriers. Serum protein concentrations in lumbar CSF increase with hyperbolic functions, but the levels of proteins that do not pass the barrier remain constant (brain proteins) or increase linearly (leptomeningal proteins). All CSF protein dynamics above and below a lumbar blockade can also be explained, independent of their barrier passage, by a reduced caudally directed flow. Local accumulation of gadolinium in multiple sclerosis (MS) is now understood as due to reduced bulk flow elimination by interstitial fluid (ISF). Nonlinear change of the steady state in barrier dysfunction and along normal rostro-caudal gradients supports the diffusion/flow model and contradicts obstructions of diffusion pathways. Regardless of the cause of the disease, pathophysiological flow blockages are found in bacterial meningitis, leukemia, meningeal carcinomatosis, Guillain-Barré syndrome, MS and experimental allergic encephalomyelitis. In humans, the fortyfold higher albumin concentrations in early fetal development decrease later with maturation of the arachnoid villi, i.e., with beginning CSF outflow, which contradicts a relevant outflow to the lymphatic system. Respiration- and heartbeat-dependent oscillations do not disturb net direction of CSF flow. Conclusion: Blood-CSF and blood-brain barrier dysfunctions are an expression of reduced CSF or ISF flow rate.

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Polyamide-Supported Covalent Organic Framework Nanomembranes for Molecular Size-Dependent Selective Separation

ACS Applied Nano Materials ◽

10.1021/acsanm.1c03279 ◽

2021 ◽

Author(s):

Yixin Yang ◽

Wende Ma ◽

Guorong Li ◽

Chao Zhong ◽

Xi Yan ◽

...

Keyword(s):

Molecular Size ◽

Selective Separation ◽

Covalent Organic Framework ◽

Size Dependent ◽

Organic Framework

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Guest molecular size-dependent inclusion complexation of parabens with cholic acid by cogrinding

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2011.08.027 ◽

2011 ◽

Vol 420 (2) ◽

pp. 191-197 ◽

Cited By ~ 4

Author(s):

Kunikazu Moribe ◽

Miyuki Masaki ◽

Ryo Kinoshita ◽

Junying Zhang ◽

Waree Limwikrant ◽

...

Keyword(s):

Cholic Acid ◽

Inclusion Complexation ◽

Molecular Size ◽

Size Dependent

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Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1616457114 ◽

2017 ◽

Vol 114 (11) ◽

pp. 2958-2963 ◽

Cited By ~ 36

Author(s):

Marlon G. Lawrence ◽

Michael K. Altenburg ◽

Ryan Sanford ◽

Julian D. Willett ◽

Benjamin Bleasdale ◽

...

Keyword(s):

Gold Nanoparticles ◽

Basement Membrane ◽

Glomerular Basement Membrane ◽

Molecular Size ◽

Slit Diaphragm ◽

Lamina Densa ◽

Electron Microscopic ◽

Proximal Tubule Cells ◽

Size Dependent ◽

Low Concentrations

How the kidney prevents urinary excretion of plasma proteins continues to be debated. Here, using unfixed whole-mount mouse kidneys, we show that fluorescent-tagged proteins and neutral dextrans permeate into the glomerular basement membrane (GBM), in general agreement with Ogston's 1958 equation describing how permeation into gels is related to molecular size. Electron-microscopic analyses of kidneys fixed seconds to hours after injecting gold-tagged albumin, negatively charged gold nanoparticles, and stable oligoclusters of gold nanoparticles show that permeation into the lamina densa of the GBM is size-sensitive. Nanoparticles comparable in size with IgG dimers do not permeate into it. IgG monomer-sized particles permeate to some extent. Albumin-sized particles permeate extensively into the lamina densa. Particles traversing the lamina densa tend to accumulate upstream of the podocyte glycocalyx that spans the slit, but none are observed upstream of the slit diaphragm. At low concentrations, ovalbumin-sized nanoparticles reach the primary filtrate, are captured by proximal tubule cells, and are endocytosed. At higher concentrations, tubular capture is saturated, and they reach the urine. In mouse models of Pierson’s or Alport’s proteinuric syndromes resulting from defects in GBM structural proteins (laminin β2 or collagen α3 IV), the GBM is irregularly swollen, the lamina densa is absent, and permeation is increased. Our observations indicate that size-dependent permeation into the lamina densa of the GBM and the podocyte glycocalyx, together with saturable tubular capture, determines which macromolecules reach the urine without the need to invoke direct size selection by the slit diaphragm.

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Permeability properties of monolayers of the human trophoblast cell line BeWo

AJP Cell Physiology ◽

10.1152/ajpcell.1997.273.5.c1596 ◽

1997 ◽

Vol 273 (5) ◽

pp. C1596-C1604 ◽

Cited By ~ 130

Author(s):

Fei Liu ◽

Michael J. Soares ◽

Kenneth L. Audus

Keyword(s):

Linoleic Acid ◽

Cell Line ◽

Morphological Changes ◽

Molecular Size ◽

Bewo Cell ◽

Human Trophoblast ◽

In Vitro System ◽

Size Dependent ◽

Bewo Cell Line

The BeWo cell line (b30 clone) has been examined as a potential in vitro system to study transplacental transport. At the light and electron microscope level, the cells were observed to form confluent monolayers on polycarbonate filters in ∼5 days and morphologically resembled the typical human trophoblast. BeWo monolayers developed a modest transepithelial electrical resistance and a molecular size-dependent permeability to hydrophilic passive diffusion markers, fluorescein, and selected fluorescein-labeled dextrans. Linoleic acid permeation across BeWo monolayers was asymmetric, saturable, and inhibited by low temperature and excess competing fatty acid. Forskolin and 8-bromoadenosine 3′,5′-cyclic monophosphate treatments stimulated morphological changes in BeWo cultures and enhanced the asymmetric passage of linoleic acid across the BeWo monolayers while having minimal effects on passive permeability, affirming that the differentiation state of the cells can influence membrane transporters and transmonolayer permeability. The basic permeability properties of the BeWo monolayers suggest that the cells grown on permeable supports may be examined as a convenient in vitro system to evaluate some transplacental transport mechanisms.

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