A Computer Evaluation of Equations for Predicting the Potential across Biological Membranes

The Goldman, Henderson, and Planck junction potential equations can be used to describe the potential across the resting giant squid axon. These equations are used to calculate the relative Na, K, and Cl permeabilities of the squid axon using the experimental measurements of Hodgkin and Katz. The equations all provide excellent agreement with the observed data and yield similar permeability values.     

Ion-pair Movement across Bilayer Membranes

WE have used bilayer lipid membranes (BLM) as models for biological membranes to study the transport of metal halides as ion-pairs. In the presence of iodine (I₂) we find¹ that various monovalent and divalent halides can readily move across BLM along a concentration gradient. The rate of transport increases as the size of the cation increases. As the membrane interior is thought to be of a liquid hydrocarbon nature, these results can be related to those of solvent extraction studies² which showed that various metal halides could be extracted efficiently from aqueous solutions into organic solvents; the extraction efficiency increases as the cation size increases.     

Mechanical Equilibrium of Biological Membranes

The nature of mechanical and electrical forces on biological membranes in relation to mechanical equilibrium is examined. The presence of a double layer of electric charge is shown to give rise to an effective pressure drop across a curved membrane of finite thickness. For certain geometric shapes of a membrane, the magnitude of the pressure drop due to electrostatic forces may set a limit on the hydrostatic pressure drop that the membrane can support without buckling. The results are applied to the equilibrium shape of the red blood cell.     

Atomic Force Microscopy of Biological Membranes

Atomic force microscopy (AFM) is an ideal method to study the surface topography of biological membranes. It allows membranes that are adsorbed to flat solid supports to be raster-scanned in physiological solutions with an atomically sharp tip. Therefore, AFM is capable of observing biological molecular machines at work. In addition, the tip can be tethered to the end of a single membrane protein, and forces acting on the tip upon its retraction indicate barriers that occur during the process of protein unfolding. Here we discuss the fundamental limitations of AFM determined by the properties of cantilevers, present aspects of sample preparation, and review results achieved on reconstituted and native biological membranes.     

The Balance of Fluid and Osmotic Pressures across Active Biological Membranes with Application to the Corneal Endothelium

The movement of fluid and solutes across biological membranes facilitates the transport of nutrients for living organisms and maintains the fluid and osmotic pressures in biological systems. Understanding the pressure balances across membranes is crucial for studying fluid and electrolyte homeostasis in living systems, and is an area of active research. In this study, a set of enhanced Kedem-Katchalsky (KK) equations is proposed to describe fluxes of water and solutes across biological membranes, and is applied to analyze the relationship between fluid and osmotic pressures, accounting for active transport mechanisms that propel substances against their concentration gradients and for fixed charges that alter ionic distributions in separated environments. The equilibrium analysis demonstrates that the proposed theory recovers the Donnan osmotic pressure and can predict the correct fluid pressure difference across membranes, a result which cannot be achieved by existing KK theories due to the neglect of fixed charges. The steady-state analysis on active membranes suggests a new pressure mechanism which balances the fluid pressure together with the osmotic pressure. The source of this pressure arises from active ionic fluxes and from interactions between solvent and solutes in membrane transport. We apply the proposed theory to study the transendothelial fluid pressure in the in vivo cornea, which is a crucial factor maintaining the hydration and transparency of the tissue. The results show the importance of the proposed pressure mechanism in mediating stromal fluid pressure and provide a new interpretation of the pressure modulation mechanism in the in vivo cornea.     

Osmotic Flow of Water across Permeable Cellulose Membranes

Direct measurements have been made of the net volume flow through cellulose membranes, due to a difference in concentration of solute across the membrane. The aqueous solutions used included solutes ranging in size from deuterated water to bovine serum albumin. For the semipermeable membrane (impermeable to the solute) the volume flow produced by the osmotic gradient is equal to the flow produced by the hydrostatic pressure RT ΔC, as given by the van't Hoff relationship. In the case in which the membrane is permeable to the solute, the net volume flow is reduced, as predicted by the theory of Staverman, based on the thermodynamics of the steady state. A means of establishing the amount of this reduction is given, depending on the size of the solute molecule and the effective pore radius of the membrane. With the help of these results, a hypothetical biological membrane moving water by osmotic and hydrostatic pressure gradients is discussed.     

Fluctuations and Fractal Noise in Biological Membranes

Our understanding of cell structure and function derives from applications of a variety of physical and life science disciplines, methods and models to an important physiological process, namely, the exchange and transport of ions and molecules across biological membranes. We know that ion transport through membranes arises from a diversity of interrelated and interactive physical and chemical phenomena over a wide range of spatial and temporal scales. Among these phenomena common to all cellular structure and function include metabolism, kinetics of molecules, chemically mediated alteration of cell membrane electrical potential, membrane ion conductance, electrical signal propagation, and modulation by chemo- and mechanoreceptive mechanisms. This review focuses on the unique information contained in fluctuations in electrical properties associated with cell membrane ion transport. Received: 19 May 2000/Revised: 10 July 2000     

Asymmetrical Lipid Bilayer Structure for Biological Membranes

IT is generally accepted that the matrix of cellular membranes is a bimolecular leaflet of phospholipid molecules in which the phospholipids are oriented so that their polar heads reside on the outer surfaces of the bilayer, in contact with the aqueous environment, the interior of the sandwich being composed of hydrophobic lipid chains^1–5. To this basic structure proteins cholesterol, glycolipids and other molecules are usually inserted in such a way as to confer on the bilayer the functional properties appropriate for the particular membrane.     

Further Observations on Asymmetrical Solute Movement across Membranes

The permeability of frog skin under the influence of urea hyperosmolarity has been studied. Flux ratio asymmetry has been demonstrated again for tracer mannitol. The inhibitors DNP, CN^-, and ouabain have been used to eliminate active sodium transport and it was found that urea hyperosmolarity produces asymmetrical mannitol fluxes on frog skins having no short-circuit current. These findings suggest that flux ratio asymmetry is due to solute interaction and is unrelated to sodium transport. Studies with a synthetic membrane show clearly that bulk flow of fluid can produce a "solvent drag" effect and change flux ratios. When bulk flow is blocked and solute gradients allowed their full expression, then solute interaction "solute drag" is easily demonstrable in a synthetic system.     

Effect of Surfactants on Diffusion of Drugs across Membranes

THE effect of surfactants on the diffusion of drugs across biological membranes and the extent of pharmacological response observed in whole organisms have been much studied¹. In a variety of organisms, including worms, goldfish and men, surfactants can both increase and decrease the rate, of drug diffusion across membranes^2–4 and although at low concentrations they enhance biological response, at higher concentrations they have the reverse effect². In addition to many naturally occurring surface active compounds, such as bile salts⁵ and phospholipids⁶, a wide variety of pharmaceutical preparations contain surfactants and, as Swisher pointed out, the vast industrial production of these compounds has resulted in their widespread occurrence throughout the biosphere⁷.     

Molecular Mechanisms of Raft Organization in Biological Membranes

Russian Journal of Bioorganic Chemistry - This review analyzes and summarizes some actual models of raft organization as dynamic structural units in lipid membranes emphasizing the discrimination...     

Temperature Dependence of Nonelectrolyte Permeation across Red Cell Membranes

The temperature dependence of permeation across human red cell membranes has been determined for a series of hydrophilic and lipophilic solutes, including urea and two methyl substituted derivatives, all the straight-chain amides from formamide through valeramide and the two isomers, isobutyramide and isovaleramide. The temperature coefficient for permeation by all the hydrophilic solutes is 12 kcal mol^-1 or less, whereas that for all the lipophilic solutes is 19 kcal mol^-1 or greater. This difference is consonant with the view that hydrophilic molecules cross the membrane by a path different from that taken by the lipophilic ones. The thermodynamic parameters associated with lipophile permeation have been studied in detail. ΔG is negative for adsorption of lipophilic amides onto an oil-water interface, whereas it is positive for transfer of the polar head from the aqueous medium to bulk lipid solvent. Application of absolute reaction rate theory makes it possible to make a clear distinction between diffusion across the water-red cell membrane interface and diffusion within the membrane. Diffusion coefficients and apparent activation enthalpies and entropies have been computed for each process. Transfer of the polar head from the solvent into the interface is characterized by ΔG^‡ = 0 kcal mol^-1 and ΔS^‡ negative, whereas both of these parameters have large positive values for diffusion within the membrane. Diffusion within the membrane is similar to what is expected for diffusion through a highly associated viscous fluid.     

Transport of Metabolites across Isolated Envelope Membranes of Spinach Chloroplasts

Isolated envelope membranes of spinach chloroplasts (Spinacia oleracea L. var. Viroflay) exhibited selective permeability. Metabolites such as 3-phosphoglycerate, bicarbonate, glyoxylate, and acetate were transported rapidly; 6-phosphogluconate, glycolate, glycine, l-malate, and succinate were intermediate; whereas glucose 6-phosphate, fructose 1,6-diphosphate, and sucrose were hardly transported. Transport rates, metabolite accumulations within the membrane vesicles, and the internal water volume of isolated and in situ envelope membranes were compared and found to show similar trends.     

Transfer times across the human body

The radioactivity disappearance curves of glucose-6-¹⁴C albumin-I¹³¹ after a single injection of tracer into a human subject have been determined in detail, particularly at early time intervals. The curves, expressed as sums of exponentials, have been analyzed as the infinite sum of convolutions of single passage time densities. The resultant transfer time distribution of a single circulatory pass allows examination of all delays in the system no matter how long they take. The structural detail evident by this means and the long mean time of a single pass of glucose (>5 min) supports the thesis that factors other than rapid and uniform diffusion play a role in the extravascular movements of glucose molecules. This study was supported by Public Health Service Grants CA 07123 from the National Cancer Institute and RR 00044 from the Division of Research Facilities and Resources, N.I.H.