Thermodynamic analysis of the permeability of biological membranes to non-electrolytes
TL;DR: The equations derived here have been applied to various permeability measurements found in the literature, such as the penetration of heavy water into animal cells, permeability of blood vessels, threshold concentration of plasmolysis and relaxation experiments with artificial membranes.
About: This article is published in Biochimica et Biophysica Acta.The article was published on 1958-01-01. It has received 1960 citations till now. The article focuses on the topics: Membrane & Permeability (earth sciences).
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TL;DR: It is shown that systemic administration of an enzymatic agent can ablate stromal HA from autochthonous murine PDA, normalize IFP, and re-expand the microvasculature and in combination with the standard chemotherapeutic, gemcitabine, the treatment permanently remodels the tumor microenvironment and consistently achieves objective tumor responses, resulting in a near doubling of overall survival.
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..., vascular and extravascular) is readily derived from fundamental thermodynamic principles (Kedem and Katchalsky, 1958; Kedem and Katchalsky, 1961; Staverman, 1952) (reviewed in Ogston and Michel, 1978) and incorporates hydrostatic and osmotic pressure gradients as the primary determinants of fluid flow, and concentration gradients as the driving force for solute flux....
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...…a semipermeable membrane dividing two compartments (e.g., vascular and extravascular) is readily derived from fundamental thermodynamic principles (Kedem and Katchalsky, 1958; Kedem and Katchalsky, 1961; Staverman, 1952) (reviewed in Ogston and Michel, 1978) and incorporates hydrostatic and…...
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TL;DR: This review summarizes and analyzes the recent data from genetic, physiological, cellular, and morphological studies that have addressed the signaling mechanisms involved in the regulation of both the paracellular and transcellular transport pathways.
Abstract: The microvascular endothelial cell monolayer localized at the critical interface between the blood and vessel wall has the vital functions of regulating tissue fluid balance and supplying the essential nutrients needed for the survival of the organism. The endothelial cell is an exquisite "sensor" that responds to diverse signals generated in the blood, subendothelium, and interacting cells. The endothelial cell is able to dynamically regulate its paracellular and transcellular pathways for transport of plasma proteins, solutes, and liquid. The semipermeable characteristic of the endothelium (which distinguishes it from the epithelium) is crucial for establishing the transendothelial protein gradient (the colloid osmotic gradient) required for tissue fluid homeostasis. Interendothelial junctions comprise a complex array of proteins in series with the extracellular matrix constituents and serve to limit the transport of albumin and other plasma proteins by the paracellular pathway. This pathway is highly regulated by the activation of specific extrinsic and intrinsic signaling pathways. Recent evidence has also highlighted the importance of the heretofore enigmatic transcellular pathway in mediating albumin transport via transcytosis. Caveolae, the vesicular carriers filled with receptor-bound and unbound free solutes, have been shown to shuttle between the vascular and extravascular spaces depositing their contents outside the cell. This review summarizes and analyzes the recent data from genetic, physiological, cellular, and morphological studies that have addressed the signaling mechanisms involved in the regulation of both the paracellular and transcellular transport pathways.
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TL;DR: It is shown that the permeability of a capillary area can be expressed by three parameters: the initial extraction of test substances added in a single injection to the blood flowing to an organ, the blood flow and the surface area of the capillaries.
Abstract: Crone, C. The permeability of capillaries in various organs as deter-mined by use of the ‘Indicator Diffusion’ method. Acta physiol. scand. 1963. 58. 292—305. — The theory of a single injection technique, the ‘Indicator Diffusion’ method, for quantitative studies of capillary permeability is developed. It is shown that the permeability of a capillary area can be expressed by three parameters: the initial extraction (E) of test substances added in a single injection to the blood flowing to an organ, the blood flow (Q) and the surface area (A) of the capillaries. The equation relating these figures is: P = (=/A) × loge1/(1—E). The permeability coefficients of capillaries in kidney, liver, lung, brain and hind limb to inulin and sucrose are reported. It is found that the permeability of capillaries varies considerably from organ to organ. It is questioned whether the pore model adequately describes the functional characteristics of the capillaries in the muscles. The existence of pores should result in a pronounced deviation of the ratio between the permeability coefficients for sucrose and inulin from the ratio between the free diffusion coefficients. This was not found to be the case.
1,114 citations
TL;DR: All SRNF-applications reported so far - in food chemistry, petrochemistry, catalysis, pharmaceutical manufacturing - will be reviewed exhaustively (324 references).
Abstract: Over the past decade, solvent resistant nanofiltration (SRNF) has gained a lot of attention, as it is a promising energy- and waste-efficient unit process to separate mixtures down to a molecular level This critical review focuses on all aspects related to this new burgeoning technology, occasionally also including literature obtained on aqueous applications or related membrane processes, if of relevance to understand SRNF better An overview of the different membrane materials and the methods to turn them into suitable SRNF-membranes will be given first The membrane transport mechanism and its modelling will receive attention in order to understand the process and the reported membrane performances better Finally, all SRNF-applications reported so far – in food chemistry, petrochemistry, catalysis, pharmaceutical manufacturing – will be reviewed exhaustively (324 references)
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TL;DR: Theoretical and experimental studies on the sieving of molecules by ultrafiltration through porous membranes indicate that an effective pore diameter of at least IOO A would be required to explain permeability of this magnitude.
Abstract: T HE PENETRATION of capillary walls by water and dissolved substances appears to take place solely by processes which require no energy transformations on the part of the capillary endothelial cells. The rate of net fluid movement across the capillary wall has been shown to be simply proportional to the difference between hydrostatic and osmotic forces acting across the capillary membranes (I, 2). The chemical composition of ascitic fluid (3), edema fluid (4) or glomerular fluid (5) closely resembles that obtainable by filtration of plasma through inert artificial membranes of suitable porosities. Filtration through peripheral capillaries, like that through artificial membranes, varies inversely with the viscosity of the filtrate as this is altered by temperature (6). These striking similarities between the permeability characteristics of living capillaries, on the one hand, and artificial porous membranes on the other, have given rise to the ‘Pore Theory’ of capillary exchange. In its simplest form, the pore theory supposes that the capillary walls are pierced with numerous ultramicroscopic openings which are in general too small to allow the passage of plasma protein molecules, but are of sufficient size and number to account for the observed rates of passage of water and nonprotein constituents of the plasma. Many important questions arise when the pore theory of capillary exchange is examined in detail. The glomerular membranes allow molecules as large as inulin (effective diffusion diameter, d, = 30 A) to pass with no detectable hindrance. Egg albumin (d, = 56 A) passes rapidly through the glomerular membranes (7-9) and even hemoglobin (d, = 62 A) is believed to pass into the glomerular filtrate in appreciable concentration (7, IO). Theoretical and experimental studies on the sieving of molecules by ultrafiltration through porous membranes (I I, 12) indicate that an effective pore diameter of at least IOO A would be required to explain permeability of this magnitude. If this is the case, how are we to imagine the physical structure of the openings in the capillary membranes? Do pores of diameter IOO A penetrate through the endothelial cells and their plasma membranes on both surfaces? Or are the openings confined to the narrow intercellular regions as postulated by Chambers and Zweifach (13)? In the latter case, is the small area available between cells sufficient to explain the observed filtration rates in such rapidly filtering systems as the kidney? If there is a distribution of pore sizes, or if water is free to
925 citations
TL;DR: A wealth of evidence supports the view that the exchange of materials through the walls of living capillaries takes place by physical processes which involve no expenditure of energy on the part of the capillary endothelial cells themselves.
Abstract: F ROM THE POINT OF VIEW of hemodynamics the blood is generally considered to circulate within a closed system of blood vessels. Even the smallest capillaries appear, under the microscope, as closed thin-walled vessels separating the blood from the extravascular fluid. Only occasionally are discontinuities in the capillary wall made evident by the diapedesis of one of the formed elements of the blood and even in such cases it is hard to be certain that a microscopically visible channel of egress is present. At high magnifications the blood appears to flow rapidly through individual capillaries thus forming a striking contrast to the relatively stagnant extravascular fluid and accentuating the role of the capillary membrane in providing a phase boundary separating the blood from the tissues. There are good reasons for supposing, however, that the capillary blood is in intimate contact with extravascular fluid and that the visible flow of blood through the capillaries is, in fact, very small in comparison with the intiWe flow of water and dissolved materials back and forth through the capillaxy walls. Evidence to be reviewed below suggests that this invisible component of the circulation takes place at a rate which is many times greater than that of the entire cardiac output. Indeed, it is by means of this ‘ultramicroscopic circulation’ through the capillary wall that the circulatory system as a whole fulfills its ultimate function in the transport of materials to and from the cells of the body. This review will deal with the physical properties of the ultramicroscopic circulation, its functional structure, the magnitude of flow through it and the physicochemical mechanisms regulating the flow. Direct methods for the study of ultrastructure have not as yet been applied to the capillary wall and much of what can be said must be deduced from quantitative studies of capillary permeability. A wealth of evidence supports the view that the exchange of materials through the walls of living capillaries takes place by physical processes which involve no expenditure of energy on the part of the capillary endothelial cells themselves. This evidence has been reviewed previously (20,30, 89, 162) and need not be considered here in detail. At least two types of capillary structure appear to be involved. On the one hand we have to consider the permeability characteristics of the plasma membranes which envelop the protoplasm of the capillary endothelial cells and which comprise the greater part of the visible capillary surface. On the basis of analogy with other known plasma membranes we may expect this type of structure to exhibit a relatively low order of permeability to ions and lipid insoluble molecules and a high order of permeability to oqgen, carbon dioxide and other lipid soluble substances. On the other hand, we have to consider specialized regions through or between endothelial cells which endow the capillary wall as a whole with a relatively high, degree of permeability to water, ions and large lipid insoluble molecules. This type of permeability resembles that of artificial porous membranes and has given rise to the hypothesis that the blood communicates directly with the extravascular fluid via channels or
858 citations