Ion Pumps Research Articles

Monovalent ions and stress-induced senescence in human mesenchymal endometrial stem/stromal cells

Monovalent ions are involved in growth, proliferation, differentiation of cells as well as in their death. This work concerns the ion homeostasis during senescence induction in human mesenchymal endometrium stem/stromal cells (hMESCs): hMESCs subjected to oxidative stress (sublethal pulse of H2O2) enter the premature senescence accompanied by persistent DNA damage, irreversible cell cycle arrest, increased expression of the cell cycle inhibitors (p53, p21) cell hypertrophy, enhanced β-galactosidase activity. Using flame photometry to estimate K+, Na+ content and Rb+ (K+) fluxes we found that during the senescence development in stress-induced hMESCs, Na+/K+pump-mediated K+ fluxes are enhanced due to the increased Na+ content in senescent cells, while ouabain-resistant K+ fluxes remain unchanged. Senescence progression is accompanied by a peculiar decrease in the K+ content in cells from 800–900 to 500–600 µmol/g. Since cardiac glycosides are offered as selective agents for eliminating senescent cells, we investigated the effect of ouabain on ion homeostasis and viability of hMESCs and found that in both proliferating and senescent hMESCs, ouabain (1 nM–1 µM) inhibited pump-mediated K+ transport (ID50 5 × 10–8 M), decreased cell K+/Na+ ratio to 0.1–0.2, however did not induce apoptosis. Comparison of the effect of ouabain on hMESCs with the literature data on the selective cytotoxic effect of cardiac glycosides on senescent or cancer cells suggests the ion pump blockade and intracellular K+ depletion should be synergized with target apoptotic signal to induce the cell death.

LPS-induced impairment of Na+/K+-ATPase activity: ameliorative effect of tannic acid in mice.

Acetylcholine is an excitatory neurotransmitter that modulates synaptic plasticity and communication, and it is essential for learning and memory processes. This neurotransmitter is hydrolyzed by acetylcholinesterase (AChE), which plays other cellular roles in processes such as inflammation and oxidative stress. Ion pumps, such as Na+/K+-ATPase and Ca2+-ATPase, are highly expressed channels that derive energy for their functions from ATP hydrolysis. Impairment of the cholinergic system and ion pumps is associated with neuropsychiatric diseases. Major depressive disorder (MDD) is an example of a complex disease with high morbidity and a heterogenous etiology. Polyphenols have been investigated for their therapeutic effects, and tannic acid (TA) has been reported to show neuroprotective and antidepressant-like activities. Animal models of depression-like behavior, such as lipopolysaccharide (LPS)-induced models of depression, are useful for investigating the pathophysiology of MDD. In this context, effects of TA were evaluated in an LPS-induced mouse model of depression-like behavior. Animals received TA for 7days, and on the last day of treatment, LPS (830μg/kg) was administered intraperitoneally. In vitro exposure of healthy brain to TA decreased the AChE activity. Additionally, this enzyme activity was decreased in cerebral cortex of LPS-treated mice. LPS injection increased the activity of Ca2+-ATPase in the cerebral cortex but decreased the enzyme activity in the hippocampus. LPS administration decreased Na+/K+-ATPase activity in the cerebral cortex, hippocampus, and striatum; however, TA administration prevented these changes. In conclusion, tannins may affect Na+/K+-ATPase and Ca2+-ATPase activities, which is interesting in the context of MDD.

Rhodopsins: An Excitingly Versatile Protein Species for Research, Development and Creative Engineering.

The first member and eponym of the rhodopsin family was identified in the 1930s as the visual pigment of the rod photoreceptor cell in the animal retina. It was found to be a membrane protein, owing its photosensitivity to the presence of a covalently bound chromophoric group. This group, derived from vitamin A, was appropriately dubbed retinal. In the 1970s a microbial counterpart of this species was discovered in an archaeon, being a membrane protein also harbouring retinal as a chromophore, and named bacteriorhodopsin. Since their discovery a photogenic panorama unfolded, where up to date new members and subspecies with a variety of light-driven functionality have been added to this family. The animal branch, meanwhile categorized as type-2 rhodopsins, turned out to form a large subclass in the superfamily of G protein-coupled receptors and are essential to multiple elements of light-dependent animal sensory physiology. The microbial branch, the type-1 rhodopsins, largely function as light-driven ion pumps or channels, but also contain sensory-active and enzyme-sustaining subspecies. In this review we will follow the development of this exciting membrane protein panorama in a representative number of highlights and will present a prospect of their extraordinary future potential.

Na+/HCO3- cotransporter 1 (nbce1) isoform gene expression during smoltification and seawater acclimation of Atlantic salmon.

The life history of Atlantic salmon (Salmo salar) includes an initial freshwater phase (parr) that precedes a springtime migration to marine environments as smolts. The development of osmoregulatory systems that will ultimately support the survival of juveniles upon entry into marine habitats is a key aspect of smoltification. While the acquisition of seawater tolerance in all euryhaline species demands the concerted activity of specific ion pumps, transporters, and channels, the contributions of Na+/HCO3- cotransporter 1 (Nbce1) to salinity acclimation remain unresolved. Here, we investigated the branchial and intestinal expression of three Na+/HCO3- cotransporter 1 isoforms, denoted nbce1.1, -1.2a, and -1.2b. Given the proposed role of Nbce1 in supporting the absorption of environmental Na+ by ionocytes, we first hypothesized that expression of a branchial nbce1 transcript (nbce1.2a) would be attenuated in salmon undergoing smoltification and following seawater exposure. In two separate years, we observed spring increases in branchial Na+/K+-ATPase activity, Na+/K+/2Cl- cotransporter 1, and cystic fibrosis transmembrane regulator 1 expression characteristic of smoltification, whereas there were no attendant changes in nbce1.2a expression. Nonetheless, branchial nbce1.2a levels were reduced in parr and smolts within 2days of seawater exposure. In the intestine, gene transcript abundance for nbce1.1 increased from spring to summer in the anterior intestine, but not in the posterior intestine or pyloric caeca, and nbce1.1 and -1.2b expression in the intestine showed season-dependent transcriptional regulation by seawater exposure. Collectively, our data indicate that tissue-specific modulation of all three nbce1 isoforms underlies adaptive responses to seawater.

Membrane Protein Activity Induces Specific Molecular Changes in Nanodiscs Monitored by FTIR Difference Spectroscopy.

It is well known that lipids neighboring integral membrane proteins directly influence their function. The opposite effect is true as well, as membrane proteins undergo structural changes after activation and thus perturb the lipidic environment. Here, we studied the interaction between these molecular machines and the lipid bilayer by observing changes in the lipid vibrational bands via FTIR spectroscopy. Membrane proteins with different functionalities have been reconstituted into lipid nanodiscs: Microbial rhodopsins that act as light-activated ion pumps (the proton pumps NsXeR and UmRh1, and the chloride pump NmHR) or as sensors (NpSRII), as well as the electron-driven cytochrome c oxidase RsCcO. The effects of the structural changes on the surrounding lipid phase are compared to mechanically induced lateral tension exerted by the light-activatable lipid analogue AzoPC. With the help of isotopologues, we show that the ν(C = O) ester band of the glycerol backbone reports on changes in the lipids’ collective state induced by mechanical changes in the transmembrane proteins. The perturbation of the nanodisc lipids seems to involve their phase and/or packing state. 13C-labeling of the scaffold protein shows that its structure also responds to the mechanical expansion of the lipid bilayer.

Animal Models of Dysregulated Cardiac Metabolism.

As a muscular pump that contracts incessantly throughout life, the heart must constantly generate cellular energy to support contractile function and fuel ionic pumps to maintain electrical homeostasis. Thus, mitochondrial metabolism of multiple metabolic substrates such as fatty acids, glucose, ketones, and lactate is essential to ensuring an uninterrupted supply of ATP. Multiple metabolic pathways converge to maintain myocardial energy homeostasis. The regulation of these cardiac metabolic pathways has been intensely studied for many decades. Rapid adaptation of these pathways is essential for mediating the myocardial adaptation to stress, and dysregulation of these pathways contributes to myocardial pathophysiology as occurs in heart failure and in metabolic disorders such as diabetes. The regulation of these pathways reflects the complex interactions of cell-specific regulatory pathways, neurohumoral signals, and changes in substrate availability in the circulation. Significant advances have been made in the ability to study metabolic regulation in the heart, and animal models have played a central role in contributing to this knowledge. This review will summarize metabolic pathways in the heart and describe their contribution to maintaining myocardial contractile function in health and disease. The review will summarize lessons learned from animal models with altered systemic metabolism and those in which specific metabolic regulatory pathways have been genetically altered within the heart. The relationship between intrinsic and extrinsic regulators of cardiac metabolism and the pathophysiology of heart failure and how these have been informed by animal models will be discussed.

A Photo-responsive Transmembrane Anion Transporter Relay.

Ion transport across lipid membranes in biology is controlled by stimuli-responsive membrane channels and molecular machine ion pumps such as ATPases. Here, we report a synthetic molecular machine-like ion transport relay, in which transporters on opposite sides of a lipid bilayer membrane facilitate transport by passing ions between them. By incorporating a photo-responsive telescopic arm into the relay design, this process is reversibly controlled in response to irradiation with blue and green light. Transport occurs only in the extended state when the length of the arm is sufficient to pass the anion between transporters located on opposite sides of the membrane. In contrast, the contracted state of the telescopic arm is too short to mediate effective transport. The system acts as a stimuli-responsive ensemble of machine-like components, reminiscent of robotic arms in a factory assembly line, working cooperatively to mediate ion transport. This work points to new prospects for using lipid bilayer membranes as scaffolds for confining, orientating, and controlling the relative positions of molecular machines, thus enabling multiple components to work in concert and opening up new applications in biological contexts.

Spontaneous and Selective Potassium Transport through a Suspended Tailor-Cut Ti3C2Tx MXene Film.

Biological ion pumps selectively transport target ions against the concentration gradient, a process that is crucial to maintaining the out-of-equilibrium states of cells. Building an ion pump with ion selectivity has been challenging. Here we show that a Ti3C2Tx MXene film suspended in air with a trapezoidal shape spontaneously pumps K+ ions from the base end to the tip end and exhibits a K+/Na+ selectivity of 4. Such a phenomenon is attributed to a range of properties of MXene. Thanks to the high stability of MXene in water and the dynamic equilibrium between evaporation and swelling, the film keeps a narrow interlayer spacing of ∼0.3 nm when its two ends are connected to reservoirs. Because of the polar electrical structure and hydrophilicity of the MXene nanosheet, K+ ions experience a low energy barrier of ∼4.6 kBT when entering these narrow interlayer spacings. Through quantitative simulations and consistent experimental results, we further show that the narrow spacings exhibit a higher energy barrier to Na+, resulting in K+/Na+ selectivity. Finally, we show that the spontaneous ion transport is driven by the asymmetric evaporation of the interlayer water across the film, a mechanism that is similar to pressure driven streaming current. This work shows how ion transport properties can be facilely manipulated by tuning the macroscopic shape of nanofluidic materials, which may attract interest in the interface of kirigami technologies and nanofluidics and show potential in energy and separation applications.

Inhibitory and stimulatory micropeptides preferentially bind to different conformations of the cardiac calcium pump

The ATP-dependent ion pump sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ in the endoplasmic reticulum to establish a reservoir for cell signaling. Because of its central importance in physiology, the activity of this transporter is tightly controlled via direct interactions with tissue-specific regulatory micropeptides that tune SERCA function to match changing physiological conditions. In the heart, the micropeptide phospholamban (PLB) inhibits SERCA, while dwarf open reading frame (DWORF) stimulates SERCA. These competing interactions determine cardiac performance by modulating the amplitude of Ca2+ signals that drive the contraction/relaxation cycle. We hypothesized that the functions of these peptides may relate to their reciprocal preferences for SERCA binding; SERCA binds PLB more avidly at low cytoplasmic [Ca2+] but binds DWORF better when [Ca2+] is high. In the present study, we demonstrated this opposing Ca2+ sensitivity is due to preferential binding of DWORF and PLB to different intermediate states that SERCA samples during the Ca2+ transport cycle. We show PLB binds best to the SERCA E1-ATP state, which prevails at low [Ca2+]. In contrast, DWORF binds most avidly to E1P and E2P states that are more populated when Ca2+ is elevated. Moreover, FRET microscopy revealed dynamic shifts in SERCA–micropeptide binding equilibria during cellular Ca2+ elevations. A computational model showed that DWORF exaggerates changes in PLB–SERCA binding during the cardiac cycle. These results suggest a mechanistic basis for inhibitory versus stimulatory micropeptide function, as well as a new role for DWORF as a modulator of dynamic oscillations of PLB–SERCA regulatory interactions.

Wound-Induced Systemic Responses and Their Coordination by Electrical Signals

Wounding not only induces the expression of damage-responsive genes, but also initiates physiological changes, such as tissue repair, vascular reconnection, and de novo organogenesis in locally damaged tissues. Wound-induced signals also propagate from the site of wounding to distal organs to elicit a systemic response. Electrical signaling, which is the most conserved type of systemic signaling in eukaryotes, is triggered by wound-induced membrane potential changes. Changes in membrane potential spread toward systemic tissues in synergy with chemical and hydraulic signals. Here, we review current knowledge on wound-induced local and systemic responses in plants. We focus particularly on how wound-activated plasma membrane-localized ion channels and pumps propagate systemic information about wounding to induce downstream molecular responses in distal tissues. Finally, we propose future studies that could lead to a better understanding of plant electrical signals and their role in physiological responses to wounding.

Optogenetics and cell replacement in retinology : Regenerative ophthalmology-What we can do!

For many degenerative retinal diseases that progressively lead to blindness, no treatment options are available so far. In recent years, several innovative therapies have been experimentally explored, which are promising because they are independent of the genetic cause of the degenerative disease. One of these is optogenetics, which involves light-sensitive proteins that selectively act as ion channels or ion pumps to control the potential of the treated cell. Thus, these cells can be stimulated or inhibited by light, quasi functionally remote controlled. In this way artificial photoreceptors are induced from the remaining cells, which has already been successfully employed in animal experiments. This type of treatment is already being tested on patients and leads to an improvement in vision, but so far only data from one patient are available. The use of optogenetics additionally requires special eyeglasses to adapt the light impulses in adequate strength and wavelength for the respective optogenes. Another exciting approach is cell replacement therapy of retinal pigment epithelium (RPE) and photoreceptor cells to exchange degenerated cell material. This appears to be very successful for RPE cells in clinical trials. Obtaining human photoreceptors from stem cells is technically possible, but very laborious. The integration of the transplanted photoreceptors into the host retinal tissue also needs further optimization for broader clinical applications; however, both cell replacement and optogenetics approaches are promising, so that the translation from basic research into clinical application will be successful.

ACYP1 Is a Pancancer Prognostic Indicator and Affects the Immune Microenvironment in LIHC.

BackgroundACYP1 plays important physiological and metabolic roles in glycolysis and membrane ion pump activity by catalyzing acyl phosphate hydrolysis. ACYP1 is related to tumorigenesis and progression and poor prognosis in gastrointestinal cancer. However, its pancancer roles and mechanisms are unclear. Our study aimed to understand the ACYP1 expression signature and prognostic value across cancers and investigate immune infiltration patterns in liver hepatocellular carcinoma (LIHC) and verify them in LIHC samples.MethodsTranscriptional expression profiles of ACYP1 across cancers were analyzed using Oncomine and TIMER. The prognostic value of ACYP1 was assessed across PrognoScan, Kaplan—Meier Plotter, and GEPIA. Significant pathways associated with ACYP1 in LIHC were obtained via Gene Set Enrichment Analysis. The correlation between ACYP1 expression and immune infiltration in LIHC was investigated using TIMER. We validated ACYP1 expression, prognostic value, and association with immune cells in tumor tissues by immunohistochemistry and flow cytometry.ResultsACYP1 was overexpressed across cancers. High expression of ACYP1 correlated with a poor prognosis in most tumor types, especially in LIHC. ACYP1 was significantly implicated in immune and metabolic related pathways. High ACYP1 expression showed significant correlations with the abundances of Th2 cells, Tregs, macrophages, dendritic cells, and myeloid-derived suppressor cells in LIHC. LIHC patients with high ACYP1 expression showed significantly shorter overall survival and relapse-free survival rates concomitant with increased infiltration of CD4+ T cells. Mouse subcutaneous tumors with ACYP1 overexpression exhibited significantly accelerated tumor progression with increased aggregation of CD4+ T cells.ConclusionOverall, ACYP1 may serve as a vital prognostic biomarker and play an immunoregulatory role in LIHC.

Metal Substrate Translocation and Transport Mechanism of the Sinorhizobium melilotiP1B‐5‐type ATPase Nia Revealed by In‐vitro Transport Assays in Proteoliposomes

P1B‐type ATPases are a class of transmembrane transporter proteins responsible for metal substrate translocation, and export across cellular membranes. These ion pumps are classified into seven sub‐families (P1B‐1‐P1B‐7‐type) based on conserved amino acid motifs in their transmembrane helices that appear to control each sub‐family’s substrate selectivity. The P1B‐5‐type sub‐family is widely found in nitrogen fixing bacteria, such as Sinorhizobium meliloti,which form a unique symbiotic relationship with legumes. This symbiotic relationship is highly dependent on the nutrition trafficking between the two species, including a tight control of transition metal homeostasis. The P1B‐5‐type ATPase Nia from S. Meliloti is recognized as a putative iron and nickel transporter, and besides possessing the typical P‐type ATPase domains and topology, it features of a C‐terminal hemerythrin‐like domain containing a di‐iron binding site involved in oxygen sensing, as proposed by in‐vivo studies. However, the substrate transport across lipid bi‐layers, the overall mechanism for cargo translocation and the transport kinetic parameters remain elusive due to lack of molecular tools to study putative substrate transport across membranes in real‐time.In this study, we coupled metal‐stimulated ATPase activity assays with an experimental platform based on multiple fluorescence sensor probes, to study substrate transport mechanism and translocation kinetics in real‐time with Nia reconstituted in a native‐like environment. We expressed and purified Nia in detergent micelles and subsequently incorporated it in artificial small unilamellar lipid bi‐layer vesicles (proteoliposomes) which allow to study the substrate specificity and transport mechanism in real‐time. The proteoliposomes were used as an in‐vitrotool to determine the kinetic parameters for metal transport by encapsulating fluorescent detector probes featuring turn‐on florescence signal upon substrate ion binding and translocation.The study revealed that Fe2+, Ni2+ and Co2+are actively translocated by Nia and the kinetic parameter analysis demonstrated that Fe2+ is the preferential Nia substrate. In parallel, by encapsulating in the proteoliposome lumen pH and membrane sensitive fluorescent probes we are also revealing the chemistry underlying the mechanism of transport and potential ions involved as counter‐transported cargos in P1B‐5‐type ATPase catalytic cycle, with the aim of revealing unique molecular features for this subclass of transmembrane metal pumps.

Bioelectricity Buzz.

Bioelectricity Buzz.

Genetic Alterations in Benign Adrenal Tumors

The genetic basis of most types of adrenal adenomas has been elucidated over the past decade, leading to the association of adrenal gland pathologies with specific molecular defects. Various genetic studies have established links between variants affecting the protein kinase A (PKA) signaling pathway and benign cortisol-producing adrenal lesions. Specifically, genetic alterations in GNAS, PRKAR1A, PRKACA, PRKACB, PDE11A, and PDE8B have been identified. The PKA signaling pathway was initially implicated in the pathogenesis of Cushing syndrome in studies aiming to understand the underlying genetic defects of the rare tumor predisposition syndromes, Carney complex, and McCune-Albright syndrome, both affected by the same pathway. In addition, germline variants in ARMC5 have been identified as a cause of primary bilateral macronodular adrenal hyperplasia. On the other hand, primary aldosteronism can be subclassified into aldosterone-producing adenomas and bilateral idiopathic hyperaldosteronism. Various genes have been reported as causative for benign aldosterone-producing adrenal lesions, including KCNJ5, CACNA1D, CACNA1H, CLCN2, ATP1A1, and ATP2B3. The majority of them encode ion channels or pumps, and genetic alterations lead to ion transport impairment and cell membrane depolarization which further increase aldosterone synthase transcription and aldosterone overproduction though activation of voltage-gated calcium channels and intracellular calcium signaling. In this work, we provide an overview of the genetic causes of benign adrenal tumors.

The role of externally-modulated electrostatic interactions in amplifying charge transport across lysine-doped peptide junctions

Many evolved biomolecular functions such as ion pumping or redox catalysis rely on controlled charge transport through the polypeptide matrix, which can be regulated by shifts in molecular protonation states and dependent supramolecular packing modes in response to environmental cues. However, the exact roles of such dynamic, non-covalent interactions in peptide charge transport have remained elusive. To tackle this challenge, here we report the modulation of charge transport in a series of lysine (Lys)-substituted hepta-glycine (Gly) peptide self-assembled monolayers (SAMs) on template-striped gold (AuTS) bottom electrodes with eutectic gallium-indium (EGaIn) liquid metal top electrodes. We demonstrate systematic modulation of hydrogen bonding and more general electrostatic interactions by shifting the position of the charged Lys-residue and creating different protonation patterns by changing the environmental pH in the AuTS/peptide//GaOx/EGaIn junctions. The effective modulation is evidenced by current density–voltage (J-V) measurements combined with SAM characterization using ultraviolet photoelectron spectroscopy (UPS) and angle-resolved X-ray photoelectron spectroscopy (ARXPS), polarization modulation–infrared reflection-absorption spectroscopy (PM-IRRAS), and molecular dynamics (MD) simulations. Decreasing the hydrogen bonding inside the peptide SAMs and increasing the electrostatic interactions by environmental counterions amplifies the charge transport differently with Lys-position, which means that the sensitive electrical response of peptide SAMs can be tuned by the peptide sequence. Our results provide insights into the relationship between molecular design and in situ modulation of charge transport properties for the development of bionanoelectronics.

IP & OEIP – Cytokinin Micro Application Modulates Root Development with High Spatial Resolution

AbstractState‐of‐the‐art technology based on organic electronics can be used as a flow‐free delivery method for organic substances with high spatial resolution. Such highly targeted drug micro applications can be used in plant research for the regulation of physiological processes on tissue and cellular levels. Here, for the first time, an organic electronic ion pump (OEIP) is reported that can transport an isoprenoid‐type cytokinin, N6‐isopentenyladenine (iP), to intact plants. Cytokinins (CKs) are plant hormones involved in many essential physiological processes, including primary root (PR) and lateral root (LR) development. Using the Arabidopsis thaliana root as a model system, efficient iP delivery is demonstrated with a biological output – cytokinin‐related PR and LR growth inhibition. The spatial resolution of iP delivery, defined for the first time for an organic compound, is shown to be less than 1 mm, exclusively affecting the OEIP‐targeted LR. Results from the application of the high‐resolution OIEP treatment method confirm previously published findings showing that the influence of CKs may vary at different stages of LR development. Thus, OEIP‐based technologies offer a novel, electronically controlled method for phytohormone delivery that could contribute to unraveling cytokinin functions during different developmental processes with high specificity.

Light-Controlled Ionic/Molecular Transport through Solid-State Nanopores and Nanochannels.

Biological nanochannels perfectly operate in organisms and exquisitely control mass transmembrane transport for complex life process. Inspired by biological nanochannels, plenty of intelligent artificial solid-state nanopores and nanochannels are constructed based on various materials and methods with the development of nanotechnology. Specially, the light-controlled nanopores/nanochannels have attracted much attention due to the unique advantages in terms of that ion and molecular transport can be regulated remotely, spatially and temporally. According to the structure and function of biological ion channels, light-controlled solid-state nanopores/nanochannels can be divided into light-regulated ion channels with ion gating and ion rectification functions, and light-driven ion pumps with active ion transport property. In this review, we present a systematic overview of light-controlled ion channels and ion pumps according to the photo-responsive components in the system. Then, the related applications of solid-state nanopores/nanochannels for molecular sensing, water purification and energy conversion are discussed. Finally, a brief conclusion and short outlook are offered for future development of the nanopore/nanochannel field.

Lens Aquaporins in Health and Disease: Location is Everything!

Cataract and presbyopia are the leading cause of vision loss and impaired vision, respectively, worldwide. Changes in lens biochemistry and physiology with age are responsible for vision impairment, yet the specific molecular changes that underpin such changes are not entirely understood. In order to preserve transparency over decades of life, the lens establishes and maintains a microcirculation system (MCS) that, through spatially localized ion pumps, induces circulation of water and nutrients into (influx) and metabolites out of (outflow and efflux) the lens. Aquaporins (AQPs) are predicted to play important roles in the establishment and maintenance of local and global water flow throughout the lens. This review discusses the structure and function of lens AQPs and, importantly, their spatial localization that is likely key to proper water flow through the MCS. Moreover, age-related changes are detailed and their predicted effects on the MCS are discussed leading to an updated MCS model. Lastly, the potential therapeutic targeting of AQPs for prevention or treatment of cataract and presbyopia is discussed.

High-pressure crystallography shows noble gas intervention into protein-lipid interaction and suggests a model for anaesthetic action

In this work we examine how small hydrophobic molecules such as inert gases interact with membrane proteins (MPs) at a molecular level. High pressure atmospheres of argon and krypton were used to produce noble gas derivatives of crystals of three well studied MPs (two different proton pumps and a sodium light-driven ion pump). The structures obtained using X-ray crystallography showed that the vast majority of argon and krypton binding sites were located on the outer hydrophobic surface of the MPs – a surface usually accommodating hydrophobic chains of annular lipids (which are known structural and functional determinants for MPs). In conformity with these results, supplementary in silico molecular dynamics (MD) analysis predicted even greater numbers of argon and krypton binding positions on MP surface within the bilayer. These results indicate a potential importance of such interactions, particularly as related to the phenomenon of noble gas-induced anaesthesia.