Properties Of Cell Membrane Research Articles

Conductance-Based Phenomenological Nonspiking Model: A Dimensionless and Simple Model That Reliably Predicts the Effects of Conductance Variations on Nonspiking Neuronal Dynamics

The modeling of single neurons has proven to be an indispensable tool in deciphering the mechanisms underlying neural dynamics and signal processing. In that sense, two types of single-neuron models are extensively used: the conductance-based models (CBMs) and the so-called phenomenological models, which are often opposed in their objectives and their use. Indeed, the first type aims to describe the biophysical properties of the neuron cell membrane that underlie the evolution of its potential, while the second one describes the macroscopic behavior of the neuron without taking into account all of its underlying physiological processes. Therefore, CBMs are often used to study "low-level" functions of neural systems, while phenomenological models are limited to the description of "high-level" functions. In this letter, we develop a numerical procedure to endow a dimensionless and simple phenomenological nonspiking model with the capability to describe the effect of conductance variations on nonspiking neuronal dynamics with high accuracy. The procedure allows determining a relationship between the dimensionless parameters of the phenomenological model and the maximal conductances of CBMs. In this way, the simple model combines the biological plausibility of CBMs with the high computational efficiency of phenomenological models, and thus may serve as a building block for studying both high-level and low-level functions of nonspiking neural networks. We also demonstrate this capability in an abstract neural network inspired by the retina and C. elegans networks, two important nonspiking nervous tissues.

Cell lipid droplet heterogeneity and altered biophysical properties induced by cell stress and metabolic imbalance

Lipid droplets (LD) are important regulators of lipid metabolism and are implicated in several diseases. However, the mechanisms underlying the roles of LD in cell pathophysiology remain elusive. Hence, new approaches that enable better characterization of LD are essential. This study establishes that Laurdan, a widely used fluorescent probe, can be used to label, quantify, and characterize changes in cell LD properties. Using lipid mixtures containing artificial LD we show that Laurdan GP depends on LD composition. Accordingly, enrichment in cholesterol esters (CE) shifts Laurdan GP from ∼0.60 to ∼0.70. Moreover, live-cell confocal microscopy shows that cells present multiple LD populations with distinctive biophysical features. The hydrophobicity and fraction of each LD population are cell type dependent and change differently in response to nutrient imbalance, cell density, and upon inhibition of LD biogenesis. The results show that cellular stress caused by increased cell density and nutrient overload increased the number of LD and their hydrophobicity and contributed to the formation of LD with very high GP values, likely enriched in CE. In contrast, nutrient deprivation was accompanied by decreased LD hydrophobicity and alterations in cell plasma membrane properties. In addition, we show that cancer cells present highly hydrophobic LD, compatible with a CE enrichment of these organelles. The distinct biophysical properties of LD contribute to the diversity of these organelles, suggesting that the specific alterations in their properties might be one of the mechanisms triggering LD pathophysiological actions and/or be related to the different mechanisms underlying LD metabolism.

Relationship between obesity, insulin resistance and cell membrane properties

Introduction and aim. The obesity is one of the greatest public health problems in developing countries and it is a triggering factor for diabetes associated with insulin resistance. The importance of cell membrane lipids as essential regulators of insulin resistance, since changes in the dynamic properties of the cell membrane (e.g., membrane fluidity), could be one of the events by which obesity affects insulin sensitivity. Thus, the insulin resistance may not only be a cause but also a consequence of lipid disorders such as dyslipidemia and/or cell membrane phospholipid composition change. The modification of plasma membrane lipid composition can change membrane biophysical properties and thus influencing protein-lipid interactions, enzymatic activity and regulation of surface receptors. Alterations in the lipid composition modify the fluidity of plasma membranes and the expression of membrane functions, such as receptor binding and enzyme activities. This review summarizes the current knowledge on the effects of the modulation of plasma membrane lipid composition and membrane fluidity in the functionality of membrane proteins involved in insulin activity, including the insulin receptor, glucose transport and Na + /K + ATPase and, in turn, the key features of the metabolic syndrome. Material and methods. References for that article were found through PubMed and Google Scholar, using terms: “obesity”, “insulin resistance” and “membrane properties”. The research was limited to abstracts and available full-text articles. Analysis of the literature. There is a strong relationship between dietary lipids, membrane lipid profiles and insulin resistance. The changes in the dynamic properties of the cell membrane (e.g., membrane fluidity), could be one of the events by which obesity affects insulin sensitivity. The modification of plasma membrane lipid composition can change membrane biophysical properties and thus influencing protein–lipid interactions, enzymatic activity, and regulation of surface receptors. Modifications of membrane phospholipid composition could have a role in the insulin action by altering membrane fluidity and, as a consequence, the insulin signaling pathway. Conclusion. As conclusion the membrane-lipid therapy approach can be used to treat important pathologies such as obesity and many others diseases such as : cancer, cardiovascular pathologies, neurodegenerative processes, obesity, metabolic disorders, inflammation, and infectious and autoimmune diseases. This pharmacological strategy aims to regulate cell functions by influencing lipid organization and membrane fluidity, inducing a concomitant modulation of membrane protein localization and activity which might serve to reverse the pathological state. Through this review we suggest an in-depth analysis of the membrane lipid therapy field, especially its molecular bases and its relevance to the development of innovative therapeutic approaches.

Effects of monolauroyl-galactosylglycerol on membrane fatty acids and properties of Bacillus cereus.

The purpose of this study was to provide new ideas for the antibacterial mechanism of monolauroyl-galactosylglycerol (MLGG) from the perspective of cell membranes. The changes in cell membrane properties of Bacillus cereus (B. cereus) CMCC 66,301 exposed to different concentrations (1 × MIC (minimum inhibitory concentration), 2 × MIC, 1 × MBC (minimum bacterial concentration)) of MLGG were evaluated. It was found that the lag phase of B. cereus cells was prolonged at low concentration MLGG (1 × MIC and 2 × MIC), while about 2 log CFU/mL reduction in B. cereus populations were observed when exposed to high concentration MLGG (1 × MBC). MLGG treated B. cereus displayed obvious membrane depolarization, while membrane permeability had no change using PI (propidium iodide) staining. Significant increase in the membrane fluidity in response to MLGG exposure occurred, which was consistent with the modification of membrane fatty acids compositions, where the relative content of straight-chain fatty acids (SCFAs) and unsaturated fatty acids (UFAs) increased, while branched-chain fatty acids (BCFAs) decreased significantly. The decreased transition Tm value and cell surface hydrophobicity was also observed. Additionally, effect of MLGG on bacterial membrane compositions were explored at the submolecular level by infrared spectroscopy. Resistance tests of B. cereus to MLGG had demonstrated the advantages of MLGG as a bacteriostatic agent. Collectively, these studies indicate that modifying the fatty acid composition and properties of cellular membranes through MLGG exposure is crucial for inhibiting bacteria growth, providing new insights into the antimicrobial mechanisms of MLGG. KEY POINTS: • Monolauroyl-galactosylglycerol inserted into B. cereus lipid bilayer membrane • Monolauroyl-galactosylglycerol treatment caused B. cereus membrane depolarization • Monolauroyl-galactosylglycerol resulted in B. cereus membrane fatty acids alteration.

Perfluoroalkyl Substances (PFAS) Affect Inflammation in Lung Cells and Tissues.

Adverse lung outcomes from exposure to per-and polyfluoroalkyl substances (PFAS) are known; however, the mechanism of action is poorly understood. To explore this, human bronchial epithelial cells were grown and exposed to varied concentrations of short-chain (perfluorobutanoic acid, perflurobutane sulfonic acid and GenX) or long-chain (PFOA and perfluorooctane sulfonic acid (PFOS)) PFAS, alone or in a mixture to identify cytotoxic concentrations. Non-cytotoxic concentrations of PFAS from this experiment were selected to assess NLRP3 inflammasome activation and priming. We found that PFOA and PFOS alone or in a mixture primed and activated the inflammasome compared with vehicle control. Atomic force microscopy showed that PFOA but not PFOS significantly altered the membrane properties of cells. RNA sequencing was performed on the lungs of mice that had consumed PFOA in drinking water for 14 weeks. Wild type (WT), PPARα knock-out (KO) and humanized PPARα (KI) were exposed to PFOA. We found that multiple inflammation- and immune-related genes were affected. Taken together, our study demonstrated that PFAS exposure could alter lung biology in a significant manner and may contribute to asthma/airway hyper-responsiveness.

Micropatterning of functional lipid bilayer assays for quantitative bioanalysis.

Interactions of the cell with its environment are mediated by the cell membrane and membrane-localized molecules. Supported lipid bilayers have enabled the recapitulation of the basic properties of cell membranes and have been broadly used to further our understanding of cellular behavior. Coupled with micropatterning techniques, lipid bilayer platforms have allowed for high throughput assays capable of performing quantitative analysis at a high spatiotemporal resolution. Here, an overview of the current methods of the lipid membrane patterning is presented. The fabrication and pattern characteristics are briefly described to present an idea of the quality and notable features of the methods, their utilizations for quantitative bioanalysis, as well as to highlight possible directions for the advanced micropatterning lipid membrane assays.

Bile Acids as Inducers of Protonophore and Ionophore Permeability of Biological and Artificial Membranes.

It is now generally accepted that the role of bile acids in the organism is not limited to their participation in the process of food digestion. Indeed, bile acids are signaling molecules and being amphiphilic compounds, are also capable of modifying the properties of cell membranes and their organelles. This review is devoted to the analysis of data on the interaction of bile acids with biological and artificial membranes, in particular, their protonophore and ionophore effects. The effects of bile acids were analyzed depending on their physicochemical properties: namely the structure of their molecules, indicators of the hydrophobic-hydrophilic balance, and the critical micelle concentration. Particular attention is paid to the interaction of bile acids with the powerhouse of cells, the mitochondria. It is of note that bile acids, in addition to their protonophore and ionophore actions, can also induce Ca2+-dependent nonspecific permeability of the inner mitochondrial membrane. We consider the unique action of ursodeoxycholic acid as an inducer of potassium conductivity of the inner mitochondrial membrane. We also discuss a possible relationship between this K+ ionophore action of ursodeoxycholic acid and its therapeutic effects.

Scanning ion conductance microscopy reveals differential effect of PM2.5 exposure on A549 lung epithelial and SH-SY5Y neuroblastoma cell membranes.

Numerous studies have linked a wide range of diseases including respiratory illnesses to harmful particulate matter (PM) emissions indoors and outdoors, such as incense PM and industrial PM. Because of their ability to penetrate the lower respiratory tract and the circulatory system, fine particles with diameters of 2.5µm or less (PM2.5) are believed to be more hazardous than larger PMs. Despite the enormous number of studies focusing on the intracellular processes associated with PM2.5 exposure, there have been limited reports studying the biophysical properties of cell membranes, such as nanoscale morphological changes induced by PM2.5. Our study assesses the membrane topographical and structural effects of PM2.5 from incense PM2.5 exposure in real time on A549 lung carcinoma epithelial cells and SH-SY5Y neuroblastoma cells that had been fixed to preclude adaptive cell responses. The size distribution and mechanical properties of the PM2.5 sample were characterized with atomic force microscopy (AFM). Nanoscale morphological monitoring of the cell membranes utilizing scanning ion conductance microscopy (SICM) indicated statistically significant increasing membrane roughness at A549 cells at half an hour of exposure and visible damage at 4h of exposure. In contrast, no significant increase in roughness was observed on SH-SY5Y cells after half an hour of PM2.5 exposure, although continued exposure to PM2.5 for up to 4h affected an expansion of lesions already present before exposure commenced. These findings suggest that A549 cell membranes are more susceptible to structural damage by PM2.5 compared to SH-SY5Y cell membranes, corroborating more enhanced susceptibility of airway epithelial cells to exposure to PM2.5 than neuronal cells.

The role of cholesterol metabolism in tumor therapy, from bench to bed.

Cholesterol and its metabolites have important biological functions. Cholesterol is able to maintain the physical properties of cell membrane, play an important role in cellular signaling, and cellular cholesterol levels reflect the dynamic balance between biosynthesis, uptake, efflux and esterification. Cholesterol metabolism participates in bile acid production and steroid hormone biosynthesis. Increasing evidence suggests a strict link between cholesterol homeostasis and tumors. Cholesterol metabolism in tumor cells is reprogrammed to differ significantly from normal cells, and disturbances of cholesterol balance also induce tumorigenesis and progression. Preclinical and clinical studies have shown that controlling cholesterol metabolism suppresses tumor growth, suggesting that targeting cholesterol metabolism may provide new possibilities for tumor therapy. In this review, we summarized the metabolic pathways of cholesterol in normal and tumor cells and reviewed the pre-clinical and clinical progression of novel tumor therapeutic strategy with the drugs targeting different stages of cholesterol metabolism from bench to bedside.

Revealing the structure and mechanisms of action of a synthetic opioid with model biological membranes at the air-water interface

Synthetic opioids such as piperazine derivative called MT-45 interact with opioid receptors in a manner similar to morphine leading to euphoria, a sense of relaxation and pain relief and are commonly used as substituents of natural opioids. In this study we show the changes in the surface properties of nasal mucosa and intestinal epithelial model cell membranes formed at the air – water interface using Langmuir technique upon the exposure to MT-45. Both membranes constitute the first barrier to absorb this substance into the human body. The presence of the piperazine derivative affects the organization of both DPPC and ternary DMPC:DMPE:DMPS monolayers treated as simple models of nasal mucosa and intestinal cell membranes, respectively. This novel psychoactive substance (NPS) leads to the fluidization of the model layers, which may indicate their increased permeability. MT-45 has a greater influence on the ternary monolayers characteristic of the intestinal epithelial cells than nasal mucosa. It might be attributed to the increased attractive interactions between the components of the ternary layer, which in turn increase the interactions with a synthetic opioid. Additionally, the crystal structures of MT-45 determined by single-crystal and powder X-ray diffraction methods allowed us to both provide useful data for facilitating the identification of synthetic opioids as well as to attribute the effect of MT-45 to the ionic interactions between protonated nitrogen atoms and negatively charged parts of the polar heads of the lipids.

A perspective on modeling pore energy and pulsed electromagnetic field induced cell membrane perforation

Pulsed electric field-induced electroporation has been widely used, but its specific perforation theory has not been fully elucidated. Therefore, this Perspective paper takes as a clue the dynamic development relationship between the pore energy and the pore state in cell membranes. First, based on the contribution of line tension, surface tension, steric repulsion, and applied electric field to pore energy, the theoretical models of reversible electroporation of a microsecond pulsed electric field and irreversible electroporation of a high-frequency nanosecond pulsed electric field are reviewed. Then, the contribution of elastic strain energy to pore energy is increased, and the theoretical model of pulsed electric field electroporation considering the mechanical properties of cell membranes is further reviewed. Based on the contribution of magnetic stress generated by the magnetic field and the gradient magnetic field to pore energy, a theoretical model of cell membrane magnetoporation under the action of a pulsed magnetic field is proposed, which lays a theoretical foundation for the popularization and application of non-contact cell membrane perforation technology.

Mechanical Properties of 3-Hydroxybutyric Acid-Induced Vesicles

The vesicle mechanical behaviors were studied upon its exposure to 3-hydroxybutyric acid using an atomic force microscope (AFM). Dipalmitoylphosphatidylcholine (DPPC) and 3-hydroxybutyric acid were used to manufacture the vesicles at their desired ratio. The deflection of an AFM probe with respect to its displacement was measured after characterizing the vesicle adsorption. The movement was analyzed with the Hertzian model to understand the physical behavior of the vesicles. However, in the deflection just prior to the first penetration, the model was a good fit, and the vesicle mechanical moduli were calculated. The moduli became lower with the higher ratio of 3-hydroxybutyric acid to DPPC, but the moduli were saturated at 0.5 of the ratio. These results appear to be the basis for the function of the metabolism associated with 3-hydroxybutyric acid, i.e., anesthetization and glycemic control, on the physical properties of cell membranes.

Hypothalamic Kisspeptin Neurons as a Target for Whole-Cell Patch-Clamp Recordings.

Kisspeptins are essential for the maturation of the hypothalamic-pituitary-gonadal (HPG) axis and fertility. Hypothalamic kisspeptin neurons located in the anteroventral periventricular nucleus and rostral periventricular nucleus, as well as the arcuate nucleus of the hypothalamus, project to gonadotrophin-releasing hormone (GnRH) neurons, among other cells. Previous studies have demonstrated that kisspeptin signaling occurs through the Kiss1 receptor (Kiss1r), ultimately exciting GnRH neuron activity. In humans and experimental animal models, kisspeptins are sufficient for inducing GnRH secretion and, consequently, luteinizing hormone (LH) and follicle stimulant hormone (FSH) release. Since kisspeptins play an essential role in reproductive functions, researchers are working to assess how the intrinsic activity of hypothalamic kisspeptin neurons contributes to reproduction-related actions and identify the primary neurotransmitters/neuromodulators capable of changing these properties. The whole-cell patch-clamp technique has become a valuable tool for investigating kisspeptin neuron activity in rodent cells. This experimental technique allows researchers to record and measure spontaneous excitatory and inhibitory ionic currents, resting membrane potential, action potential firing, and other electrophysiological properties of cell membranes. In the present study, crucial aspects of the whole-cell patch-clamp technique, known as electrophysiological measurements that define hypothalamic kisspeptin neurons, and a discussion of relevant issues about the technique, are reviewed.

Recent progress in cancer cell membrane-based nanoparticles for biomedical applications.

Immune clearance and insufficient targeting have limited the efficacy of existing therapeutic strategies for cancer. Toxic side effects and individual differences in response to treatment have further limited the benefits of clinical treatment for patients. Biomimetic cancer cell membrane-based nanotechnology has provided a new approach for biomedicine to overcome these obstacles. Biomimetic nanoparticles exhibit various effects (e.g., homotypic targeting, prolonging drug circulation, regulating the immune system, and penetrating biological barriers) after encapsulation by cancer cell membranes. The sensitivity and specificity of diagnostic methods will also be improved by utilizing the properties of cancer cell membranes. In this review, different properties and functions of cancer cell membranes are presented. Utilizing these advantages, nanoparticles can exhibit unique therapeutic capabilities in various types of diseases, such as solid tumors, hematological malignancies, immune system diseases, and cardiovascular diseases. Furthermore, cancer cell membrane-encapsulated nanoparticles show improved effectiveness and efficiency in combination with current diagnostic and therapeutic methods, which will contribute to the development of individualized treatments. This strategy has promising clinical translation prospects, and the associated challenges are discussed.

Conductive Antifouling Sensing Coating: A Bionic Design Inspired by Natural Cell Membrane.

Constructing antifouling coatings for biosensing interfaces is a major hurdle in driving their practical application. Inspired by the excellent antifouling properties of natural cell membranes, a conductive biomimetic antifouling interface coating is proposed, which highly mimics the excellent antifouling properties of biofilms while overcoming the low conductivity defects of conventional coatings. Polyethylene glycol-Au gel is selected as the support structure and electron transfer layer, on which phospholipids and ampholytes are applied to construct a hydration layer for antifouling. The coating maintains promisingly low adsorption in biological matrices such as whole blood, serum, and urine, and has been utilized to construct multimodal clinical assay systems that provide favorable concordance with clinical results. Thus, this conductive bio-coating breaks the last barrier of biosensors toward practical applications and possesses extremely significant application value.

Effect of Anionic Lipids on Mammalian Plasma Cell Membrane Properties.

The effect of lipid composition on models of the inner leaflet of mammalian cell membranes has been investigated. Grazing incidence X-ray diffraction and X-ray and neutron reflectivity have been used to characterize lipid packing and solvation, while electrochemical and infrared spectroscopic methods have been employed to probe phase behavior in an applied electric field. Introducing a small quantity of the anionic lipid dimyristoylphosphatidylserine (DMPS) into bilayers of zwitterionic dimyristoylphosphatidylethanolamine (DMPE) results in a significant change in the bilayer response to an applied field: the tilt of the hydrocarbon chains increases before returning to the original tilt angle on detachment of the bilayer. Equimolar mixtures, with slightly closer chain packing, exhibit a similar but weaker response. The latter also tend to incorporate more solvent during this electrochemical phase transition, at levels similar to those of pure DMPS. Reflectivity measurements reveal greater solvation of lipid layers for DMPS > 30 mol %, matching the greater propensity for DMPS-rich bilayers to incorporate water. Taken together, the data indicate that the range of 10-35 mol % DMPS provides optimum bilayer properties (in flexibility and function as a barrier), which may explain why the DMPS content of cell membranes tends to be found within this range.

Distribution of cholesterol in asymmetric membranes driven by composition and differential stress.

Phospholipid asymmetry appears to be an evolutionarily conserved property of eukaryotic plasma membranes, suggesting it is crucial for their structure and function. It is fundamentally a non-equilibrium phenomenon since it can decay by lipids ‘‘flip-flopping’’ between leaflets. Cells must therefore maintain it by a variety of active mechanisms. This is easy for regular phospholipids, whose flip-flop takes hours/days but difficult for cholesterol, where these timescales are in the microsecond range. Cholesterol affects many properties of lipid membranes, from their elastic response to emergence of rafts in multi-component mixtures. It is therefore distressing that we know so little about its trans-membrane partitioning. We propose a theoretical model for the distribution of cholesterol in asymmetric membranes, focusing on the interplay of two dominant effects-difference in lipid composition, which leads to a partitioning bias in cholesterol, and lateral stress arising from crowding one leaflet with respect to the other. To test our theory, we employed coarse grained molecular dynamics simulations performed using the Cooke model. We find that our theory, which accounts for various elastic and thermodynamic drivers, explains the trends in our simulations. We show that the presence of cholesterol does not automatically result in tensionless membranes, even in the absence of preferential partitioning of this species. Additionally, we find that cholesterol's solvation bias can balance phospholipid number asymmetry, which results in strong correlations between cholesterol asymmetry and differential stress. Applying our theory to the most recent data on human RBC membranes suggests that close to 90% of all cholesterol resides in the exoplasmic leaflet, with a large remaining differential stress. This calls into question the notion of rafts being exoplasmic domains connected to liquid-ordered/liquid-disordered phase coexistence and forces us to rethink the common textbook picture of plasma membranes.

Single-particle tracking and machine-learning classification reveals heterogeneous Piezo1 diffusion.

The mechanically-activated ion channel Piezo1 is involved in numerous physiological processes. Piezo1 is activated by diverse mechanical cues and is gated by membrane tension. The channel has been found to be mobile in the plasma membrane. We employed single particle tracking (SPT) of endogenously-expressed, tdTomato-tagged Piezo1 using Total Internal Reflection Fluorescence Microscopy in two cell types, mouse embryonic fibroblasts and liver sinusoidal endothelial cells. Application of SPT unveiled a surprising heterogeneity of Piezo1 mobility in the plasma membrane. Leveraging a machine learning technique, Piezo1 trajectories were sorted into distinct classes (“mobile,” “intermediate,” and “trapped”) by partitioning features that describe the geometric properties of a trajectory. To evaluate the effects of the plasma membrane properties on Piezo1 diffusion, we manipulated membrane composition by depleting or supplementing cholesterol or by adding margaric acid to stiffen the membrane. To address effects of channel activation on Piezo1 mobility, we treated cells with Yoda1, a Piezo1 agonist, and GsMTx-4, a channel inhibitor. We collected thousands of trajectories for each condition, and found that “mobile” Piezo1 in cells supplemented with cholesterol or margaric acid exhibited decreased mobility, whereas Piezo1 in cholesterol-depleted membranes demonstrated increased mobility, compared to their respective controls. Additionally, activation by Yoda1 increased Piezo1 mobility and inhibition by GsMTx-4 decreased Piezo1 mobility compared to their respective controls. The “mobile” trajectories were analyzed further by fitting the time-averaged mean-squared displacement as a function of lag time to a power-law model, revealing Piezo1 consistently exhibits anomalous subdiffusion. This suggests Piezo1 is not freely mobile, but that its mobility may be hindered by subcellular interactions. These studies illuminate the fundamental properties governing Piezo1 diffusion in the plasma membrane and set the stage to determine how specific cellular interactions may influence channel activity and mobility.

QCM‐D Study of the Formation of Solid‐Supported Artificial Lipid Membranes: State‐of‐the‐Art, Recent Advances, and Perspectives

Solid‐supported lipid bilayers (SLBs) are excellent platforms for studying the biophysical properties of cell membranes. Among the existing approaches used to form SLBs, vesicle fusion and rupture onto solid supports are most commonly employed owing to their straightforward procedure. The current understanding of the mechanisms behind this approach has greatly benefited from the use of surface‐sensitive techniques, especially quartz crystal microbalance with dissipation monitoring (QCM‐D) in combination with other analytical techniques, such as atomic force microscopy (AFM) or localized surface plasmon resonance (LSPR). Herein, an overview of the pathways of vesicle adsorption and rupture under various experimental conditions is provided. Examples including recent findings of how the variation of the properties of lipid vesicles (size, charge), aqueous buffer (pH, ionic strength, osmotic pressure), and solid support (surface energy) affect the pathway mechanism of adsorption and rupture are provided. Recent reports on poorly understood properties such as surface roughness and topography are provided, together with the need for further studies relevant to biomimetic and sensing purposes.

Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a disease that claims ~1.6 million lives annually. The current treatment regime is long and expensive, and missed doses contribute to drug resistance. Therefore, development of new anti-TB drugs remains one of the highest public health priorities. Mtb has evolved a complex cell envelope that represents a formidable barrier to antibiotics. The Mtb cell envelop consists of four distinct layers enriched for Mtb specific lipids and glycans. Although the outer membrane, comprised of mycolic acid esters, has been extensively studied, less is known about the plasma membrane, which also plays a critical role in impacting antibiotic efficacy. The Mtb plasma membrane has a unique lipid composition, with mannosylated phosphatidylinositol lipids (phosphatidyl-myoinositol mannosides, PIMs) comprising more than 50% of the lipids. However, the role of PIMs in the structure and function of the membrane remains elusive. Here, we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the biophysical properties of mycobacterial plasma membranes. We assess both symmetric and asymmetric assemblies of the Mtb plasma membrane and compare this with residue distributions of Mtb integral membrane protein structures. To further validate the model, we tested known anti-TB drugs and demonstrated that our models agree with experimental results. Thus, our work sheds new light on the organization of the mycobacterial plasma membrane. This paves the way for future studies on antibiotic development and understanding Mtb membrane protein function.