-
Advances in Physiology Education Jun 2017Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the...
Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the cell's interior. The selectively permeable nature of the cell membrane allows the movement of some solutes and prevents the movement of others. This has important consequences for cell volume and the integrity of the cell and, as a result, is of utmost clinical importance, for example in the administration of isotonic intravenous infusions. The concepts of osmolarity and tonicity are often confused by students as impermeant isosmotic solutes such as NaCl are also isotonic; however, isosmotic solutes such as urea are actually hypotonic due to the permeant nature of the membrane. By placing red blood cells in solutions of differing osmolarities and tonicities, this experiment demonstrates the effects of osmosis and the resultant changes in cell volume. Using hemoglobin standard solutions, where known concentrations of hemoglobin are produced, the proportion of hemolysis and the effect of this on resultant hematocrit can be estimated. No change in cell volume occurs in isotonic NaCl, and, by placing blood cells in hypotonic NaCl, incomplete hemolysis occurs. By changing the bathing solution to either distilled water or isosmotic urea, complete hemolysis occurs due to their hypotonic effects. With the use of animal blood in this practical, students gain useful experience in handling tissue fluids and calculating dilutions and can appreciate the science behind clinical scenarios.
Topics: Animals; Erythrocytes; Hemolysis; Osmosis; Physiology; Sodium Chloride; Students; Urea
PubMed: 28526694
DOI: 10.1152/advan.00083.2016 -
Advances in Physiology Education Dec 2018Understanding osmolarity and tonicity is one of the more challenging endeavors undertaken by students of the natural sciences. We asked students who completed a course...
Understanding osmolarity and tonicity is one of the more challenging endeavors undertaken by students of the natural sciences. We asked students who completed a course in animal physiology to submit an essay explaining what they found most perplexing about this subject, and what in-class activities proved most useful to them. Students had difficulty distinguishing osmolarity from tonicity and determining tonicity based on the solution's composition. The most useful activities were questions requiring simultaneous consideration of both osmolarity and tonicity. Problems that require calculating osmotic concentration and the volumes of body fluid compartments after administration or loss of various solutions emphasize the significance of osmolarity and tonicity in the context of systemic homeostasis and clinical medicine. We hope that our approach to teaching osmolarity and tonicity will prove useful to physiology lecturers who are looking for new ways of introducing this complicated topic to their health professions students.
Topics: Animals; Cell Size; Humans; Learning; Osmolar Concentration; Osmosis; Physiology; Students, Health Occupations; Teaching
PubMed: 30303411
DOI: 10.1152/advan.00094.2018 -
Cellular and Molecular Life Sciences :... Feb 2015Plants often encounter unfavorable environmental conditions because of their sessile lifestyle. These adverse factors greatly affect the geographic distribution of... (Review)
Review
Plants often encounter unfavorable environmental conditions because of their sessile lifestyle. These adverse factors greatly affect the geographic distribution of plants, as well as their growth and productivity. Drought stress is one of the premier limitations to global agricultural production due to the complexity of the water-limiting environment and changing climate. Plants have evolved a series of mechanisms at the morphological, physiological, biochemical, cellular, and molecular levels to overcome water deficit or drought stress conditions. The drought resistance of plants can be divided into four basic types-drought avoidance, drought tolerance, drought escape, and drought recovery. Various drought-related traits, including root traits, leaf traits, osmotic adjustment capabilities, water potential, ABA content, and stability of the cell membrane, have been used as indicators to evaluate the drought resistance of plants. In the last decade, scientists have investigated the genetic and molecular mechanisms of drought resistance to enhance the drought resistance of various crops, and significant progress has been made with regard to drought avoidance and drought tolerance. With increasing knowledge to comprehensively decipher the complicated mechanisms of drought resistance in model plants, it still remains an enormous challenge to develop water-saving and drought-resistant crops to cope with the water shortage and increasing demand for food production in the future.
Topics: Antioxidants; Droughts; Gene Expression Regulation, Plant; Osmosis; Oxidative Stress; Photosynthesis; Plant Leaves; Plant Roots; Plants; Plants, Genetically Modified
PubMed: 25336153
DOI: 10.1007/s00018-014-1767-0 -
Nature Cell Biology Sep 2020Ferroptosis is a regulated form of necrotic cell death that is caused by the accumulation of oxidized phospholipids, leading to membrane damage and cell lysis. Although...
Ferroptosis is a regulated form of necrotic cell death that is caused by the accumulation of oxidized phospholipids, leading to membrane damage and cell lysis. Although other types of necrotic death such as pyroptosis and necroptosis are mediated by active mechanisms of execution, ferroptosis is thought to result from the accumulation of unrepaired cell damage. Previous studies have suggested that ferroptosis has the ability to spread through cell populations in a wave-like manner, resulting in a distinct spatiotemporal pattern of cell death. Here we investigate the mechanism of ferroptosis execution and discover that ferroptotic cell rupture is mediated by plasma membrane pores, similarly to cell lysis in pyroptosis and necroptosis. We further find that intercellular propagation of death occurs following treatment with some ferroptosis-inducing agents, including erastin and C' dot nanoparticles, but not upon direct inhibition of the ferroptosis-inhibiting enzyme glutathione peroxidase 4 (GPX4). Propagation of a ferroptosis-inducing signal occurs upstream of cell rupture and involves the spreading of a cell swelling effect through cell populations in a lipid peroxide- and iron-dependent manner.
Topics: Cell Death; Cell Line, Tumor; Ferroptosis; HeLa Cells; Humans; Iron; MCF-7 Cells; Necrosis; Osmosis; Phospholipid Hydroperoxide Glutathione Peroxidase; U937 Cells
PubMed: 32868903
DOI: 10.1038/s41556-020-0565-1 -
Cell Feb 2018The extracellular space (ECS) of the brain has an extremely complex spatial organization, which has defied conventional light microscopy. Consequently, despite a marked...
The extracellular space (ECS) of the brain has an extremely complex spatial organization, which has defied conventional light microscopy. Consequently, despite a marked interest in the physiological roles of brain ECS, its structure and dynamics remain largely inaccessible for experimenters. We combined 3D-STED microscopy and fluorescent labeling of the extracellular fluid to develop super-resolution shadow imaging (SUSHI) of brain ECS in living organotypic brain slices. SUSHI enables quantitative analysis of ECS structure and reveals dynamics on multiple scales in response to a variety of physiological stimuli. Because SUSHI produces sharp negative images of all cellular structures, it also enables unbiased imaging of unlabeled brain cells with respect to their anatomical context. Moreover, the extracellular labeling strategy greatly alleviates problems of photobleaching and phototoxicity associated with traditional imaging approaches. As a straightforward variant of STED microscopy, SUSHI provides unprecedented access to the structure and dynamics of live brain ECS and neuropil.
Topics: Animals; Brain; Cell Movement; Coloring Agents; Electrophysiological Phenomena; Epilepsy; Extracellular Space; Female; Glutamates; Imaging, Three-Dimensional; Male; Mice, Inbred C57BL; Neurons; Neuropil; Osmosis; Synapses
PubMed: 29474910
DOI: 10.1016/j.cell.2018.02.007 -
Journal of Neural Engineering Jun 2021Our laboratory has proposed chemical stimulation of retinal neurons using exogenous glutamate as a biomimetic strategy for treating vision loss caused by photoreceptor...
Our laboratory has proposed chemical stimulation of retinal neurons using exogenous glutamate as a biomimetic strategy for treating vision loss caused by photoreceptor (PR) degenerative diseases. Although our previousstudies using pneumatic actuation indicate that chemical retinal stimulation is achievable, an actuation technology that is amenable to microfabrication, as needed for animplantable device, has yet to be realized. In this study, we sought to evaluate electroosmotic flow (EOF) as a mechanism for delivering small quantities of glutamate to the retina. EOF has great potential for miniaturization.An EOF device to dispense small quantities of glutamate was constructed and its ability to drive retinal output tested in anpreparation of PR degenerate rat retina.We built and tested an EOF microfluidic system, with 3D printed and off-the-shelf components, capable of injecting small volumes of glutamate in a pulsatile fashion when a low voltage control signal was applied. With this device, we produced excitatory and inhibitory spike rate responses in PR degenerate rat retinae. Glutamate evoked spike rate responses were also observed to be voltage-dependent and localized to the site of injection.The EOF device performed similarly to a previously tested conventional pneumatic microinjector as a means of chemically stimulating the retina while eliminating the moving plunger of the pneumatic microinjector that would be difficult to miniaturize and parallelize. Although not implantable, the prototype device presented here as a proof of concept indicates that a retinal prosthetic based on EOF-driven chemical stimulation is a viable and worthwhile goal. EOF should have similar advantages for controlled dispensing of charged neurochemicals at any neural interface.
Topics: Animals; Biomimetics; Electroosmosis; Glutamic Acid; Photoreceptor Cells; Rats; Retina
PubMed: 33984848
DOI: 10.1088/1741-2552/ac00d3 -
Biochimica Et Biophysica Acta.... Apr 2022The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating... (Review)
Review
The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating the diffusion of small polar solutes. AQPs have been recognised as drug targets for a variety of disorders associated with disrupted water or solute transport, including brain oedema following stroke or trauma, epilepsy, cancer cell migration and tumour angiogenesis, metabolic disorders, and inflammation. Despite this, drug discovery for AQPs has made little progress due to a lack of reproducible high-throughput assays and difficulties with the druggability of AQP proteins. However, recent studies have suggested that targetting the trafficking of AQP proteins to the plasma membrane is a viable alternative drug target to direct inhibition of the water-conducting pore. Here we review the literature on the trafficking of mammalian AQPs with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis.
Topics: Animals; Aquaporins; Cell Membrane; Humans; Osmosis; Plants; Protein Isoforms; Protein Transport; Water
PubMed: 34973181
DOI: 10.1016/j.bbamem.2021.183853 -
Bioconjugate Chemistry Feb 2019Intracellular delivery of biological agents such as peptides, proteins, and nucleic acids generally rely on the endocytic pathway as the major uptake mechanism,... (Review)
Review
Intracellular delivery of biological agents such as peptides, proteins, and nucleic acids generally rely on the endocytic pathway as the major uptake mechanism, resulting in their entrapment inside the endosome and lysosome. The recent discovery of cell-penetrating molecules of exceptionally high endosomal escape and cytosolic delivery efficiencies and elucidation of their mechanism of action represent major breakthroughs in this field. In this Topical Review, we provide an overview of the recent progress in understanding and enhancing the endosomal escape process and the new opportunities opened up by these recent findings.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Endosomes; Humans; Membrane Fusion; Osmosis; Peptides; Pharmaceutical Preparations
PubMed: 30525488
DOI: 10.1021/acs.bioconjchem.8b00778 -
Pediatric Nephrology (Berlin, Germany) Oct 2017Introduction of the so-called biocompatible peritoneal dialysis (PD) fluids was based on a large body of experimental evidence and various clinical trials suggesting... (Review)
Review
Introduction of the so-called biocompatible peritoneal dialysis (PD) fluids was based on a large body of experimental evidence and various clinical trials suggesting important clinical benefits. Of these, until now, only preservation of residual renal function-likely due to lower glucose degradation product load and, in case of icodextrin, improved fluid and blood pressure control-have consistently been proven, whereas the impact on important clinical endpoints such as infectious complications, preservation of PD membrane transport function, and patient outcome, are still debated. In view of the high morbidity and mortality rates of PD patients, novel approaches are warranted and comprise the search for alternative osmotic agents and enrichment of PD fluids with specific pharmacologic agents, such as alanyl-glutamine, potentially counteracting local but also systemic sequelae of uremia and PD.
Topics: Biocompatible Materials; Blood Pressure; Dialysis Solutions; Glucose; Health Services Needs and Demand; Humans; Icodextrin; Kidney Failure, Chronic; Osmosis; Peritoneal Dialysis; Peritoneum; Treatment Outcome
PubMed: 27722783
DOI: 10.1007/s00467-016-3461-y -
Water Research Oct 2022Organic micropollutants (OMPs) in drinking water constitute a potential risk to human health; therefore, effective removal of these pollutants is required.... (Review)
Review
Organic micropollutants (OMPs) in drinking water constitute a potential risk to human health; therefore, effective removal of these pollutants is required. Nanofiltration (NF) and reverse osmosis (RO) are promising membrane-based technologies to remove OMPs. In NF and RO, the rejection of OMPs depends on the properties and characteristics of the membrane, the solute, and the solution. In this review, we discuss how these properties can be included in models to study and predict the rejection of OMPs. Initially, an OMP classification is proposed to capture the relevant properties of 58 OMPs. Following the methodology described in this study, more and new OMPs can be easily included in this classification. The classification aims to increase the comprehension and mechanistic understanding of OMP removal. Based on the physicochemical principles used to classify the 58 OMPs, it is expected that other OMPs in the same groups will be similarly rejected. From this classification, we present an overview of the rejection mechanisms involved in the removal of specific OMP groups. For instance, we discuss the removal of OMPs classified as perfluoroalkyl substances (e.g., perfluorooctanoic acid, PFOA). These substances are highly relevant due to their human toxicity at extremely low concentration as well as their persistence and omnipresence in the environment. Finally, we discuss how the rejection of OMPs can be predicted by describing both the membrane-solution interface and calculating the transport of solutes inside the membrane. We illustrate the importance and impact of different rejection mechanisms and interfacial phenomena on OMP removal and propose an extended Nernst-Plank equation to calculate the transport of solutes across the membrane due to convection, diffusion, and electromigration. Finally, we show how the theory discussed in this review leads to improved predictions of OMP rejection by the membranes.
Topics: Humans; Water Purification; Drinking Water; Fluorocarbons; Osmosis; Filtration; Membranes, Artificial; Solutions; Environmental Pollutants; Water Pollutants, Chemical
PubMed: 36240724
DOI: 10.1016/j.watres.2022.119130