Changes In Membrane Properties Research Articles

Membrane property changes in most distal motor axons in chronic inflammatory demyelinating polyneuropathy.

Distal nerve terminals, where the blood-nerve barrier is anatomically deficient, are preferentially affected in immune-mediated neuropathies. Excitability alterations near the motor nerve terminals may be more prominent than the nerve trunk in typical chronic inflammatory demyelinating polyneuropathy (CIDP). In 20 patients with typical CIDP, motor nerve excitability testing was performed at the motor point and wrist of the ulnar nerve, and results were compared with those in 20 healthy persons. Chronic inflammatory demyelinating polyneuropathy patients showed greater threshold changes in hyperpolarizing threshold electrotonus at the motor point (P < .05) but not at the wrist. Strength-duration time constant did not show significant differences between CIDP and controls at both sites. Axonal property changes in CIDP are more prominent in distal portions of axons compared with the nerve trunk, presumably due to salient demyelination near the distal nerve terminals. Motor point excitability measurements could elucidate underlying pathophysiology in immune-mediated neuropathies.

Peptide-bicelle interaction: Following variations in size and morphology by a combined NMR-SAXS approach

Changes in membrane properties occurring upon protein interaction are key questions in understanding membrane protein function. To report on the occurring size and shape variation we present here a combined NMR-SAXS method performed under physiological conditions using the same samples, enabling determination of a global parameter, the hydration radius (rH) and estimating the bicelle shape. We use zwitterionic (DMPC/DHPC) and negatively charged (DMPC/DHPC/DMPG) bicelles and investigate the interaction with model transmembrane and surface active peptides (KALP23 and melittin). 1H NMR measurements based mostly on the translational diffusion coefficient D determination are used to characterize cmc values of DHPC micelles under the investigated conditions, to describe DHPC distribution with exact determination of the q (long chain/short chain) lipid ratio, to estimate aggregation numbers and effective rH values. The scattering curve is used to fit a lenticular core-shell model enabling us to describe the bicelle shape in terms of ellipsoidal axis length parameters. For all studied systems formation of oblate ellipsoids is found. Even though the rG/rH ratio would be an elegant way to characterize shape variations, we show that changes occurring upon peptide-bicelle interaction in the “effective” size and in the measure on the anisometry - morphology - of the objects can be described by using rH and the simplistic ellipsoidal core-shell model. While the influence of the transmembrane KALP peptide is significant, effects upon addition of surface active melittin peptide seem negligible. This synergy of techniques under controlled conditions can provide information about bicellar shape modulation occurring during peptide-bicelle interactions.

Envisioned role of slit bypass pores in physical aging of carbon molecular sieve membranes

Carbon molecular sieve (CMS) hollow fibers are a special class of rigid, molecular sieving membranes with unique scalability and excellent separation properties for challenging gas-pairs. These high-performing membranes are subject to moderate productivity losses and selectivity gains over time via a phenomenon typically referred to as physical aging. This article considers the role of slit bypass pores in physical aging as sensed by membrane property changes of CMS derived from aromatic polyimide precursors. Such pores are believed to be edge imperfections between adjacent ultramicroporous plates that may tighten over time, causing a reduction in penetrant diffusion coefficients. The envisioned mechanism leading to such slit bypass pores and their effects on penetrant transport are considered here from a fundamental perspective. Importantly, these slit bypass pores can be manipulated to suppress physical aging in CMS hollow fiber membranes, therefore enabling attractive long-term separation properties for multiple challenging applications.

Replacing plasma membrane outer leaflet lipids with exogenous lipid without damaging membrane integrity.

We recently introduced a MαCD-based method to efficiently replace virtually the entire population of plasma membrane outer leaflet phospholipids and sphingolipids of cultured mammalian cells with exogenous lipids (Li et al, (2016) Proc. Natl. Acad. Sci USA 113:14025-14030). Here, we show if the lipid-to- MαCD ratio is too high or low, cells can round up and develop membrane leakiness. We found that this cell damage can be reversed/prevented if cells are allowed to recover from the exchange step by incubation in complete growth medium. After exchange and transfer to complete growth medium cell growth was similar to that of untreated cells. In some cases, cell damage was also prevented by carrying out exchange at close to room temperature (rather than at 37°C). Exchange with lipids that do (sphingomyelin) or do not (unsaturated phosphatidylcholine) support a high level of membrane order in lipid vesicles had the analogous effect on plasma membrane order, confirming exogenous lipid localization in the plasma membrane. Importantly, changes in lipid composition and plasma membrane properties after exchange and recovery persisted for several hours. Thus, it should be possible to use lipid exchange to investigate the effect of plasma membrane lipid composition upon several aspects of membrane structure and function.

Peripheral Antimicrobial Peptide Gomesin Induces Membrane Protrusion, Folding, and Laceration.

Optical microscopy shows that the peripheral antimicrobial peptide (AMP) gomesin does not disrupt the bacterial membrane by forming stable transmembrane pores but induces lipid accumulation domains, which is followed by a sudden burst near the domains. The molecular action mechanisms of gomesin on vesicle and planar bilayer membranes are investigated in this work using coarse-grained molecular dynamics simulations. By comparing the membrane morphology and property changes induced by gomesin and the pore-forming AMP melittin, we determined that the amphiphilic shape of the AMPs is a key factor affecting the mechanism of cell death. The binding of wedge-shaped gomesin, with a small hydrophobic surface, onto the membrane induces protrusion and folding of the outer monolayer followed by sudden membrane lacerations at the axillae of the protuberances. Alternatively, cylinder-shaped melittins with comparable hydrophilic and hydrophobic surfaces destroy membranes by forming stable pores coexisting with exocytosis-like buddings and endocytosis-like invaginations. The multiple actions of AMPs on the bacterial membrane suggest diverse paradigms for designing molecular carriers for delivering drugs to the cell.

Enhancement of desalination performance of thin-film nanocomposite membrane by cellulose nanofibers

The incorporation of nanoparticles in a polymer membrane has been recognised as an effective strategy to improve the membrane performance in water processing. However, the leaching of nanoparticles from the membrane is potentially a concern as it may lead to the change of membrane properties and contamination of treated water. In this work, 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized cellulose nanofibers (CNFs) were for the first time incorporated into the polyamide layer of thin film composite (TFC) reverse osmosis (RO) membrane during interfacial polymerization to improve its membrane performance. CNFs are made from renewable and sustainable resources and they are non-toxic and environmentally friendly. The optimal loading of CNFs within the TFC membrane enhanced the permeance of the fabricated membranes by more than 50% (29.8 L m−2 h−1 at operating pressure of 1.5 MPa), whilst retaining high NaCl rejection at 96.2%. Chlorine stability test results indicated that the nanocomposite membranes showed better chlorine resistance performance than bare TFC membranes. This work successfully demonstrated the potential use of CNFs as a low cost and non-toxic filler to improve the performance of RO membranes for water desalination.

Effect of multi-modal environmental stress on dose-dependent cytotoxicity of nanodiamonds in Saccharomyces cerevisiae cells

A tremendous increase in the use of functionalised nanomaterials for industrial processes and consumer products inevitably promotes their interaction with living organisms and environment. Previous studies have investigated cell-nanoparticle interactions under conditions otherwise favourable for cell survival and proliferation, yet in real life, organisms are subject to environmental stresses, which may affect their response to nanoparticles. This work investigates the effect of atmospheric-pressure plasma, a model stress inducing environment rich in highly-reactive ROS and RNS species, UV light, and mild heat, on the interactions between inert nanodiamond particles (NDs) and a eukaryotic model organism, Saccharomyces cerevisiae. Plasma treatment significantly affected nanoparticle uptake attributed to changes in membrane properties. Accumulation of nanoparticles in larger deposits inside the cells and around the cell wall affected cell survival and proliferation. Plasma-treated cells exposed to 100 μg ml−1 NDs for 24 h showed significant inhibition of metabolic activity and 55% reduction in cell viability, whereas at lower concentrations (0, 5 and 50 μg ml−1) of NDs, no significant effect on cell viability or cell growth was observed. These results suggest that presence of intra- or extra-cellular stresses is an important determinant of cell fate upon exposure to nanoparticles.

MISFOLDING AND EARLY AGGREGATION OF AMYLOID β42 PROTEIN: THE CRITICAL ROLE OF MEMBRANES

Even with growing evidence for the involvement of Aβ oligomers in the development of Alzheimer's disease (AD), very limited knowledge exists regarding the molecular mechanisms behind the protein aggregation processes for Aβ. The amyloid cascade hypothesis posits that the onset of diseases due to protein aggregation involves the spontaneous assembly of an amyloidogenic polypeptide. However, there is a serious complication with translating current knowledge on amyloid aggregation in vitro to understanding the aggregation process in vivo. We combined AFM imaging and high-power computational approaches to elucidate a molecular mechanism of aggregation of Aβ42 on membranes. We have discovered that interaction of Aβ42 with membranes allows for Aβ42 to assemble in oligomers at the physiological concentration range. We were able to directly visualize a spontaneous assembly of Aβ42 aggregates on the membrane bilayers. Importantly, this aggregation process is dynamic, so the assembled aggregates can dissociate from the surface into the bulk solution and play roles of seeds for aggregation in the bulk solution, or start a neurotoxic effect such as phosphorylation of the tau protein to initiate its misfolding and aggregation. To elucidate a molecular mechanism underlying the on-surface aggregation process, we applied computational modeling (all-atom Molecular Dynamic simulations). The simulations demonstrate that the interaction with the membrane surface dramatically changes the conformation of Aβ42 protein allowing for the formation of long aggregation–prone β-sheet structures never observed for Aβ42 protein in solution. We posit that on-membrane aggregation is the mechanism by which neurotoxic amyloid aggregates are assembled under physiological conditions. We propose a model in which amyloid aggregation is linked with elevated synthesis of amyloid proteins. A change in membrane properties leading to an increase in affinity of amyloid proteins to the membrane surface facilitates the assembly of stable oligomers. The proposed model is a significant departure from the current model as it directs the development of treatments and preventions towards approaches that control the cell membranes composition to prevent the on-surface aggregation process.

Aging and HIV-1 alter the function of specific K+ channels in prefrontal cortex pyramidal neurons

The medial prefrontal cortex (mPFC) is a key regulator of neurocognition. The glutamatergic pyramidal neurons are the predominant component of neurons in the mPFC. Aging and HIV profoundly alter the structure and function of mPFC pyramidal neurons, including, but are not limited to, dysregulation of NMDA receptors and voltage-gated calcium channels. Here we assessed the impact of aging and in vivo HIV exposure on the functional activity (firing) of mPFC pyramidal neurons mediated by voltage-gated K+ (Kv) channels and inwardly-rectifying K+ (Kir) channels using patch-clamp recording in rat brain slices ex vivo. We found that aging and HIV significantly affect firing in different manners by altering the activity of Kv and likely Kir channels, associated with changes in membrane properties and the mRNA levels of specific Kv channels. Evoked firing was significantly decreased in mPFC neurons of older (12 month, 12 m) rats compared to younger (6/7 week, 6/7wk) rats, regardless of HIV status. In contrast, firing was significantly increased in neurons from Tg rats compared to non-Tg rats, regardless of age. Aging/HIV-induced alterations in firing were mediated by dysfunctional Kv channels and Kir channels, which exhibit significant changes in their activity and/or expression induced by aging and HIV exposure in vivo. Collectively, these novel findings demonstrate that aging is associated with a significant decline of mPFC neuronal activity; while long-term HIV exposure in vivo could drive mPFC neurons from over-activation to loss of firing, which could ultimately exacerbate the decline of mPFC neuronal activity.

Membrane phospholipid alteration causes chronic ER stress through early degradation of homeostatic ER-resident proteins

Phospholipid homeostasis in biological membranes is essential to maintain functions of organelles such as the endoplasmic reticulum. Phospholipid perturbation has been associated to cellular stress responses. However, in most cases, the implication of membrane lipid changes to homeostatic cellular response has not been clearly defined. Previously, we reported that Saccharomyces cerevisiae adapts to lipid bilayer stress by upregulating several protein quality control pathways such as the endoplasmic reticulum-associated degradation (ERAD) pathway and the unfolded protein response (UPR). Surprisingly, we observed certain ER-resident transmembrane proteins, which form part of the UPR programme, to be destabilised under lipid bilayer stress. Among these, the protein translocon subunit Sbh1 was prematurely degraded by membrane stiffening at the ER. Moreover, our findings suggest that the Doa10 complex recognises free Sbh1 that becomes increasingly accessible during lipid bilayer stress, perhaps due to the change in ER membrane properties. Premature removal of key ER-resident transmembrane proteins might be an underlying cause of chronic ER stress as a result of lipid bilayer stress.

Unveiling the Modulating Role of Extracellular pH in Permeation and Accumulation of Small Molecules in Subcellular Compartments of Gram-negative Escherichia coli using Nonlinear Spectroscopy.

Quantitative evaluation of small molecule permeation and accumulation in Gram-negative bacteria is important for drug development against these bacteria. While these measurements are commonly performed at physiological pH, Escherichia coli and many other Enterobacteriaceae infect human gastrointestinal and urinary tracts, where they encounter different pH conditions. To understand how external pH affects permeation and accumulation of small molecules in E. coli cells, we apply second harmonic generation (SHG) spectroscopy using SHG-active antimicrobial compound malachite green as the probe molecule. Using SHG, we quantify periplasmic and cytoplasmic accumulations separately in live E. coli cells, which was never done before. Compartment-wise measurements reveal accumulation of the probe molecule in cytoplasm at physiological and alkaline pH, while entrapment in periplasm at weakly acidic pH and retention in external solution at highly acidic pH. Behind such disparity in localizations, up to 2 orders of magnitude reduction in permeability across the inner membrane at weakly acidic pH and outer membrane at highly acidic pH are found to play key roles. Our results unequivocally demonstrate the control of external pH over entry and compartment-wise distribution of small molecules in E. coli cells, which is a vital information and should be taken into account in antibiotic screening against E. coli and other Enterobacteriaceae members. In addition, our results demonstrate the ability of malachite green as an excellent SHG-indicator of changes of individual cell membrane and periplasm properties of live E. coli cells in response to external pH change from acidic to alkaline. This finding, too, has great importance, as there is barely any other molecular probe that can provide similar information.

(255) Effects of Cannabinoids on Responses of Human Dorsal Root Ganglia Neurons

Cannabinoids are suggested to be a potentially important alternative approach to analgesia. Rodent models have shown analgesic properties of cannabinoid receptor activation and suppressed nociceptive responses within sensory neurons. The goal of the present study was to determine whether activation of cannabinoid receptors in human sensory neurons could suppress nociceptive responses or hyperactivity. Lumbar level human dorsal root ganglia were recovered from cadaveric organ donors at the University of Cincinnati Medical Center, dissociated and cultured, or fixed and frozen for histology. Using Fura-2AM calcium imaging of viable human sensory neurons, responses to the peripherally active cannabinoid agonist CB-13, a potent CB1/CB2 agonist, in naive neurons were examined. Responses to capsaicin (250 nM) in presence and absence of the inflammatory mediator PGE2 (1 µM) were examined after pre-treatment with 1 µM CB-13, or with CB-13 bath applied in between capsaicin administrations. Our results show that CB-13 produced no calcium influx in sensory neurons on its own, and that responses to capsaicin in naive neurons as well as PGE2-exposed neurons were not altered by CB-13. Patch clamp recordings of human sensory neurons to test changes in membrane properties by cannabinoid receptor activation by CB-13 is reported. Our data do not presently support the concept of peripherally acting cannabinoid receptors as having the capacity to suppress sensory neuron nociceptive responses or sensitization in people.

Modeling Pseudomonas aeruginosa Inner Plasma Membrane in Planktonic and Biofilm Modes

Pseudomonas aeruginosa changes its growth modes under different conditions. The bacteria in biofilm is more resistant to environmental stress compared to the planktonic mode of growth. The compositions of the inner plasma membrane for the two modes are noticeably different. Major lipid types are chosen from experiment to model the membrane in both modes of growth, and molecular dynamics simulation is used to study the properties of the membrane. The CHARMM36 lipid force field is used and tested against several experimental results. Our models include lipids containing cyclopropane in the middle of the sn-2 tail, namely, 1-palmitoyl-2-cis-11,12-methylene-stearic-acid-sn-glycero-3-phosphoethanolamine and 1-palmitoyl-2-cis-11,12-methylene-stearic-acid-sn-glycero-3-phosphoglycerol. The PE:PG ratio for the two model membranes is close, but the fraction of lipids composed of long-chain and cyclopropane-containing fatty acids changes significantly, causing differences between the two models. Compared to previous model membranes built for Escherichia coli, the inner membrane of P. aeruginosa has a longer averaged lipid tail length and a higher percentage of PG lipids, which are responsible for the changes in membrane properties like membrane thickness and stiffness. Most importantly, the comparison to experiments shows good agreements and encourages the model's use to study the behavior of proteins from P. aeruginosa associated with the membrane.

Effects of phase transformation on properties of alumina ceramic membrane: A new assessment based on quantitative X-ray diffraction (QXRD)

Alumina ceramic membranes were synthesized by pressing boehmite into disc form and sintering at different temperatures. Quantitative X-ray diffraction (QXRD) analysis was firstly used for determining the compositions of different types of alumina in membrane products. The result quantitative determined that alumina membranes experienced a series of phase transition from boehmite → γ-alumina → δ-alumina → θ-alumina → α-alumina from 450 to 1300 °C. Below 850 °C, no significant alumina transformation (i.e. γ-alumina was the dominate phase) was detected in fabricated membranes, which corresponded to stable membrane properties (i.e. porosity, BET surface area, pore size and chemical stability). At 950–1300 °C, substantial phase transformation was detected as follows, θ-alumina significantly increased from 1.21 to 61.6% (950–1125 °C), and α-alumina increased gradually from 3.98 to 100% (1100–1300 °C). Accordingly, the substantial phase transformation lead to the significant change in membrane properties at 950–1300 °C. Lower temperature (1150 °C) membrane containing 8.2% θ-alumina and 91.8% α-alumina showed comparable properties with 1300 °C consist of 100% α-alumina sintered products due to the similar alumina composition in the products. The overall results indicated that the properties of membrane were accordingly determined by the structure and content of alumina phases in membrane products. This strategy proposed a valuable method for production of lower temperature alumina-based ceramic membrane.

Structural Changes and Operational Deterioration of the Uf Polyethersulfone (Pes) Membrane Due to Chemical Cleaning

Microfiltration (MF) and ultrafiltration (UF) membranes are capable of rejecting most of particulate and colloidal matter from natural water. The major impediment to their applications is fouling caused by contaminants that accumulate on and/or inside the membrane. Therefore, most membranes are subjected to chemical cleaning procedures as one of the methods to control fouling. Exposure to chemical cleaning agents can reduce the performance and lead to the degradation of polyethersulfone (PES) ultrafiltration membranes. This study was conducted in order to evaluate the effect of cleaning agents on the properties of the PES membranes during exposure to short-term foulant and a cleaning agent. The cleaning agents evaluated were NaOH, HCl and NaOCl. The accelerated static cleaning conditions showed significant changes in PES flat sheet membrane properties in case of cleaning with NaOCl. These changes were analyzed using SEM microscopy, FTIR spectroscopy, contact angle measurement and hydraulic membrane performance evaluation.

Impact of triclosan adaptation on membrane properties, efflux and antimicrobial resistance of Escherichia coli clinical isolates.

Analysing the effect of step-wise exposure of Escherichia coli isolates to sublethal concentrations of triclosan (TCS) that is widely used as an antiseptic, preservative and disinfectant. Changes in the tolerance to the biocide itself and the cross-resistance to clinically important antibiotics were analysed. The involvement of efflux mechanism was studied as well as the possible implication of modifications in cytoplasmic membrane properties including integrity, permeability, potential and depolarization in the resistance mechanisms. Most of E.coli isolates that were adapted to TCS showed increased antimicrobial resistance, lower outer and inner membrane permeability, higher membrane depolarization, more negative membrane potential and enhanced efflux activity using qRT-PCR. Nonsignificant change in membrane integrity was found in the adapted cells. This study suggests that the extensive use of TCS at sublethal concentrations contributed to the emergence of antibiotic resistance in E.coli clinical isolates, by inducing changes in bacterial membrane properties and enhancing the efflux system. The extensive usage of TCS has a deleterious effect on the spread of antibiotic resistance, and more studies are needed to investigate the molecular mechanisms underlying the effects of TCS.

Sphingosine 1-phosphate-mediated activation of ezrin-radixin-moesin proteins contributes to cytoskeletal remodeling and changes of membrane properties in epithelial otic vesicle progenitors

Hearing loss is among the most prevalent sensory impairments in humans. Cochlear implantable devices represent the current therapies for hearing loss but have various shortcomings. ERM (ezrin- radixin -moesin) are a family of adaptor proteins that link plasma membrane with actin cytoskeleton, playing a crucial role in cell morphology and in the formation of membrane protrusions. Recently, bioactive sphingolipids have emerged as regulators of ERM proteins. Sphingosine 1-phosphate (S1P) is a pleiotropic sphingolipid which regulates fundamental cellular functions such as proliferation, survival, migration as well as processes such as development and inflammation mainly via ligation to its specific receptors S1PR (S1P1–5). Experimental findings demonstrate a key role for S1P signaling axis in the maintenance of auditory function. Preservation of cellular junctions is a fundamental function both for S1P and ERM proteins, crucial for the maintenance of cochlear integrity. In the present work, S1P was found to activate ERM in a S1P2-dependent manner in murine auditory epithelial progenitors US/VOT-E36. S1P-induced ERM activation potently contributed to actin cytoskeletal remodeling and to the appearance of ionic currents and membrane passive properties changes typical of more differentiated cells. Moreover, PKC and Akt activation was found to mediate S1P-induced ERM phosphorylation. The obtained findings contribute to demonstrate the role of S1P signaling pathway in inner ear biology and to disclose potential innovative therapeutical approaches in the field of hearing loss prevention and treatment.

Altered sleep architecture, rapid eye movement sleep, and neural oscillation in a mouse model of human chromosome 16p11.2 microdeletion.

Sleep abnormalities are common among children with neurodevelopmental disorders. The human chr16p11.2 microdeletion is associated with a range of neurological and neurobehavioral abnormalities. Previous studies of a mouse model of human chr16p11.2 microdeletion (chr16p11.2df/+) have demonstrated pathophysiological changes at the synapses in the hippocampus and striatum; however, the impact of this genetic abnormality on system level brain functions, such as sleep and neural oscillation, has not been adequately investigated. Here, we show that chr16p11.2df/+ mice have altered sleep architecture, with increased wake time and reduced time in rapid eye movement (REM) and non-REM (NREM) sleep. Importantly, several measurements of REM sleep are significantly changed in deletion mice. The REM bout number and the bout number ratio of REM to NREM are decreased in mutant mice, suggesting a deficit in REM-NREM transition. The average REM bout duration is shorter in mutant mice, indicating a defect in REM maintenance. In addition, whole-cell patch clamp recording of the ventrolateral periaqueductal gray (vlPAG)-projecting gamma-aminobutyric acid (GABA)ergic neurons in the lateral paragigantocellular nucleus of ventral medulla of mutant mice reveal that these neurons, which are important for NREM-REM transition and REM maintenance, have hyperpolarized resting membrane potential and increased membrane resistance. These changes in intrinsic membrane properties suggest that these projection-specific neurons of mutant mice are less excitable, and thereby may play a role in deficient NREM-REM transition and REM maintenance. Furthermore, mutant mice exhibit changes in neural oscillation involving multiple frequency classes in several vigilance states. The most significant alterations occur in the theta frequency during wake and REM sleep.

Modeling Pseudomonas aeruginosa inner plasma membrane in planktonic and biofilm modes.

Pseudomonas aeruginosa changes its growth modes under different conditions. The bacteria in biofilm is more resistant to environmental stress compared to the planktonic mode of growth. The compositions of the inner plasma membrane for the two modes are noticeably different. Major lipid types are chosen from experiment to model the membrane in both modes of growth, and molecular dynamics simulation is used to study the properties of the membrane. The CHARMM36 lipid force field is used and tested against several experimental results. Our models include lipids containing cyclopropane in the middle of the sn-2 tail, namely, 1-palmitoyl-2-cis-11,12-methylene-stearic-acid-sn-glycero-3-phosphoethanolamine and 1-palmitoyl-2-cis-11,12-methylene-stearic-acid-sn-glycero-3-phosphoglycerol. The PE:PG ratio for the two model membranes is close, but the fraction of lipids composed of long-chain and cyclopropane-containing fatty acids changes significantly, causing differences between the two models. Compared to previous model membranes built for Escherichia coli, the inner membrane of P. aeruginosa has a longer averaged lipid tail length and a higher percentage of PG lipids, which are responsible for the changes in membrane properties like membrane thickness and stiffness. Most importantly, the comparison to experiments shows good agreements and encourages the model's use to study the behavior of proteins from P. aeruginosa associated with the membrane.

Changes in physicochemical properties of kidney cells membrane as a consequence of hypertension and treatment of hypertensive rats with FAAH inhibitor

Hypertension is a civilization disease leading to remodeling and damage of blood vessels, impaired renal function and premature death. The aim of this study was to compare the effect of chronic administration of URB597, the FAAH (fatty acid amide hydrolase) inhibitor, to rats with primary (SHRs) and secondary (DOCA-salt hypertensive rats) hypertension on electrical and physicochemical properties of kidney cells membranes. Changes in the electrical charge of the membrane may affect the cell functions. The electrical properties of the kidney cells (surface charge density, zeta potential) were measured by electrophoresis. Qualitative and quantitative composition of the membrane (phospholipids and proteins) was determined by HPLC and lipid peroxidation product (4-hydroxy-2E-hexenal; 4-HHE) level was examined by GCMSMS, while the sialic acid content was measured by resorcinol method. In rats with primary hypertension (SHR) and secondary hypertension (DOCA-salt), changes in electrical properties (increase of electric charge and zeta potential) and membrane composition (increase in sialic acid and protein concentration and decrease in phospholipid level) of kidney cells are observed in comparison to control animals. Greater changes were observed in DOCA-salt hypertensive rats. Changes in membrane properties caused by URB597 depend on the type of hypertension. The administration of URB597 to rats with primary hypertension partially prevents changes in the electrical properties (electrical charge, zeta potential) of the membrane caused by hypertension as well as in the sialic acid and proteins content. However, there is no reduction in oxidative stress, assessed by the level of 4-HHE, which may affect the metabolic function of the kidneys. URB597 administered to rats with DOCA salt does not prevent, but rather intensifies, changes caused by hypertension in the kidney. In conclusion, URB597 given to individuals with hypertension, particularly with secondary hypertension, enhancing some disturbances in electric and physicochemical properties of kidney cells observed in hypertension what may lead to additional kidney disorders. Therefore, further researches are necessary.