Hollow fiber membranes of PCL and PCL/graphene as scaffolds with potential to develop in vitro blood–brain barrier models

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood–brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. A biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, which may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.This research was funded by IDIVAL (INNVAL 17/20), MINECO/EIG-Concert Japan (X-MEM PCI2018-092929 project, International Joint Program 2018) and MINECO/Spain Feder (CTM-2016-75509-R project)

Hollow Fiber Membranes of PCL and PCL/Graphene as Scaffolds with Potential to Develop In Vitro Blood—Brain Barrier Models

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood–brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. A biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, which may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.This research was funded by IDIVAL (INNVAL 17/20), MINECO/EIG-Concert Japan (X-MEM PCI2018-092929 project, International Joint Program 2018) and MINECO/Spain Feder (CTM-2016-75509-R project)

Resting and excited states of biological membrane

In recent years, a vast body of information has been accummulated on the electrical properties of biological membranes. It has been found that electrical potential differences occur across them, that ions can penetrate them and that they have a quite high resistance to the flow of electric current through them. Analysis of this information has revealed that there is no general theory of membrane phenomena which can explain all of it. As well as these general phenomena, some cell membranes, particularily those of nerve cells, are capable of producing a temporary and localised change in membrane potential and membrane resistance, which is propagated along the membrane as an electrical impulse.An excitable membrane is nowadays regarded as being one of the basic functional units in a biological computer or control system and in view of its fundamental importance, it is hardly surprising that probably more information is available on the electrical properties of nerve membranes (particularily the giant nerve from the squid) than on any other membrane. A great deal is now known about the action potential, as the phenomenon of exitability is called, and despite the illuminating hypothesis of Hodgkin and Huxley, the problem of the exact physical chemical mechanism of excitability remains to be solved.All nerves are capable of conducting impulses and so are muscle cells; so also are certain. giant plant cells of the Characeae. Over the years the development of knowledge about the action potential in nerve has proceeded side by side with the study of the action potential in these plant cells and in this thesis the giant plant cell Nitella translucens has been chosen for studying biological membranes in both their resting and excited states. This chapter is concerned mainly with the theoretical basis of electrical phenomena in membranes in general, and with the electrical properties of biological membranes in particular

Electrical Properties of Model Lipid Membranes

Biological membranes are essential components of the living systems and processes occurring with their participation are related mainly to electric phenomena, such as signal transduction, the existence of membrane potentials, and transport through the membrane. It is well known that the universal model of the cell membrane structure is the lipid bilayer, which constitutes the environment for integral and surface membrane proteins. Thus, much attention has been given to the study of the organization and properties of these structures concerning both experimental and theoretical aspects. As systematic examinations are impeded by the complexity of the natural membranes, the best approach to conducting detailed physical and chemical studies of biological membranes is to use simplified well-defined model lipid membranes. Among the most commonly used are liposomes, planar lipid membranes, membranes on solid substrates, and lipid monolayers on the free surface.Studies of the electrical properties of model lipid membranes have been carried out for many years. However, there are still many issues that have not been verified experimentally and for which the existing results are incomplete or inconsistent. Therefore, the main objective of this book was to collect recent scientific and review articles on the electrical properties of model lipid membranes. This objective has been successfully achieved, for which I express heartfelt appreciation to all authors and reviewers for their excellent contributions

Electrical phenomena in the nephron

The epithelia lining the nephron form single cell layers that manifest distinctive physical properties such as transepithelial electrical potential differences and electrical conductances. The electrical behavior of epithelia is important to the understanding of ion movements across these structures since these are seen as electric current and ultimately depend on their conjugate force, the electrochemical potential difference and a membrane property, the ionic conductance.In addition to earlier reviews [1, 2] we have recently surveyed electrical potential differences and resistances of renal tubules [3]. The majority of the presently available experimental data are derived from observations that treat the epithelium as a single diffusion barrier. However, transepithelial flows cannot be adequately understood from a description of the electrical properties of the full epithelial layer. First, morphologically renal epithelia constitute multicompartmental systems where several ion diffusion boundaries, in series or in parallel, exist rather than a single one. Moreover, electrolyte flows may appear macroscopically as electroneutral while, at the microscopic level of a single barrier, electroneutrality may be violated. Finally, electrochemical potential gradients across a complete epithelium may imply the active or passive nature of ion movements whereas entirely different inferences would follow from the driving forces that govern individual intraepithelial barriers.The present study aims at an explanation of overall transepithelial electrical phenomena as a function of the discrete electrical characteristics of single barriers, more often single cell membranes. Clearly the cell membrane approach is only one level of analysis more advanced than the overall epithelial approach. Thin biological membranes are presently treated as black-boxes because of our lack of a molecular description of ion permeation channels within the membrane phase itself. Thus, the level of understanding of renal transport processes at which we aim in this paper remains essentially phenomenological in nature. In the following we will successively discuss electrical potential differences, electrical conductances and, finally, how these properties control ion flows through single barriers or through the full epithelial thickness. In each instance our focus will be on the single boundaries of tubule cells.The only segments that have been investigated at the single membrane level are the proximal convoluted, distal and cortical collecting tubule [3]. As a rule intracellular impalements by means of microelectrodes are a prerequisite for information about individual cell membranes. Amphibian preparations such as Necturus, Triturus or Amphiuma are most useful because of the large size and less extensive basal infoldings of the tubule cells. Potentials in mammalian cells can be studied in vivo but only after extensive immobilization of the kidney [4, 5], in kidney slices [6] or in isolated tubules [7]

The Effect of the Nonlinearity of the Response of Lipid Membranes to Voltage Perturbations on the Interpretation of Their Electrical Properties. A New Theoretical Description

Our understanding of the electrical properties of cell membranes is derived from experiments where the membrane is exposed to a perturbation (in the form of a time-dependent voltage or current change) and information is extracted from the measured output. The interpretation of such electrical recordings consists in finding an electronic equivalent that would show the same or similar response as the biological system. In general, however, there is no unique circuit configuration, which can explain a single electrical recording and the choice of an electric model for a biological system is based on complementary information (most commonly structural information) of the system investigated. Most of the electrophysiological data on cell membranes address the functional role of protein channels while assuming that the lipid matrix is an insulator with constant capacitance. However, close to their melting transition the lipid bilayers are no inert insulators. Their conductivity and their capacitance are nonlinear functions of both voltage, area and volume density. This has to be considered when interpreting electrical data. Here we show how electric data commonly interpreted as gating currents of proteins and inductance can be explained by the nonlinear dynamics of the lipid matrix itself

Application of electrochemical impedance for characterising arrays of Bi2S3 nanowires

Electrochemical Impedance Spectroscopy (EIS) was used to characterise the electrical properties of bismuth sulphide (Bi2S3) nanowires (NWs) templated within anodic aluminium oxide (AAO) membranes. A specially engineered cell, with a nominal electrolyte volume of 0.1–0.2 ml, was used to hold and measure the electrochemical impedance of the fragile NW/AAO samples. An equivalent circuit model was developed to determine the filling density of nanowires within the porous templates. The EIS method can be utilised to probe the nanowire filling density in porous membranes over large sample areas, which is often unobtainable using electron microscopy and conductive atomic force microscopy techniques

Application of electrochemical impedance for characterising arrays of Bi2S3 nanowires

Electrochemical Impedance Spectroscopy (EIS) was used to characterise the electrical properties of bismuth sulphide (Bi2S3) nanowires (NWs) templated within anodic aluminium oxide (AAO) membranes. A specially engineered cell, with a nominal electrolyte volume of 0.1–0.2 ml, was used to hold and measure the electrochemical impedance of the fragile NW/AAO samples. An equivalent circuit model was developed to determine the filling density of nanowires within the porous templates. The EIS method can be utilised to probe the nanowire filling density in porous membranes over large sample areas, which is often unobtainable using electron microscopy and conductive atomic force microscopy techniques