Cell membranes sustain phospholipid imbalance via cholesterol asymmetry.

Membranes are molecular interfaces that compartmentalize cells to control the flow of nutrients and information. These functions are facilitated by diverse collections of lipids, nearly all of which are distributed asymmetrically between the two bilayer leaflets. Most models of biomembrane structure and function often include the implicit assumption that these leaflets have similar abundances of phospholipids.

Applications of phase-separating multi-bilayers in protein-membrane domain interactions.

Synthetic model membranes are important tools to elucidate lipid domain and protein interactions due to predefined lipid compositions and characterizable biophysical properties. Here, we introduce a model membrane with multiple lipid bilayers (multi-bilayers) stacked on a mica substrate that is prepared through a spin-coating technique. The spin-coated multi-bilayers are useful in the study of phase separated membranes with a high cholesterol content, mobile lipids, microscopic and reversible phase separation, and easy conjugation with proteins, which make them a good model to study interactions between proteins and membrane domains.

Membrane lipids couple synaptotagmin to SNARE-mediated granule fusion in insulin-secreting cells.

Insulin secretion depends on the Ca-regulated fusion of granules with the plasma membrane. A recent model of Ca-triggered exocytosis in secretory cells proposes that lipids in the plasma membrane couple the calcium sensor Syt1 to the membrane fusion machinery (Kiessling , 2018). Specifically, Ca-mediated binding of Syt1's C2 domains to the cell membrane shifts the membrane-anchored SNARE syntaxin-1a to a more fusogenic conformation, straightening its juxtamembrane linker.

Coupling of protein condensates to ordered lipid domains determines functional membrane organization.

During T cell activation, the transmembrane adaptor protein LAT (linker for activation of T cells) forms biomolecular condensates with Grb2 and Sos1, facilitating signaling. LAT has also been associated with cholesterol-rich condensed lipid domains; However, the potential coupling between protein condensation and lipid phase separation and its role in organizing T cell signaling were unknown. Here, we report that LAT/Grb2/Sos1 condensates reconstituted on model membranes can induce and template lipid domains, indicating strong coupling between lipid- and protein-based phase separation.

Rab3 mediates a pathway for endocytic sorting and plasma membrane recycling of ordered microdomains.

The composition of the plasma membrane (PM) must be tightly controlled despite constant, rapid endocytosis, which requires active, selective recycling of endocytosed membrane components. For many proteins, the mechanisms, pathways, and determinants of this PM recycling remain unknown. We report that association with ordered, lipid-driven membrane microdomains (known as rafts) is sufficient for PM localization of a subset of transmembrane proteins and that abrogation of raft association disrupts their trafficking and leads to degradation in lysosomes.

Effects of electroacupuncture with dexmedetomidine on myocardial ischemia/reperfusion injury in rats.

Background: To investigate the protective effect of electroacupuncture combined with dexmedetomidine (EA + Dex) on oxidative stress injury in myocardial ischemia/reperfusion (I/R) rats.

Methods: A total of 50 male Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation (sham group); I/R group; dexmedetomidine group (Dex group); electroacupuncture group (EA group); and EA + Dex group. The myocardial I/R model was established.

Mitochondrion, lysosome, and endoplasmic reticulum: Which is the best target for phototherapy?

Photodynamic therapy (PDT) is a robust cancer treatment modality, and the precise spatiotemporal control of its subcellular action site is crucial for its effectiveness. However, accurate comparison of the efficacy of different organelle-targeted PDT approaches is challenging since it is difficult to find a single system that can achieve separate targeting of different organelles with separable time windows and similar binding amounts. Herein, we conjugated chlorin e6 (Ce6) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (ammonium salt) (DSPE-PEG-NH) to afford DSPE-PEG-Ce6, which could migrate from mitochondrion to lysosome and ultimately to endoplasmic reticulum (ER) after cellular internalization.

Membrane Heterogeneity Beyond the Plasma Membrane.

The structure and organization of cellular membranes have received intense interest, particularly in investigations of the raft hypothesis. The vast majority of these investigations have focused on the plasma membrane of mammalian cells, yielding significant progress in understanding membrane heterogeneity in terms of lipid composition, molecular structure, dynamic regulation, and functional relevance. In contrast, investigations on lipid organization in other membrane systems have been comparatively scarce, despite the likely relevance of membrane domains in these contexts.

Palladium Nanosheets as Safe Radiosensitizers for Radiotherapy.

Many noble metal-based nanoparticles have emerged for applications in cancer radiotherapy in recent years, but few investigations have been carried out for palladium nanoparticles. Herein, palladium nanosheets (Pd NSs), which possess a sheetlike morphology with a diameter of ∼14 nm and a thickness of ∼2 nm, were utilized as a sensitizer to improve the performance of radiotherapy. It was found that Pd NSs alone did not decrease the cell viability after treatment for as long as 130 h, suggesting the excellent cytocompatibility of the nanoagents.

Sequential Treatment of Cell Cycle Regulator and Nanoradiosensitizer Achieves Enhanced Radiotherapeutic Outcome.

Nanoradiosensitizers are promising agents for enhancing cancer radiotherapeutic efficiency. Although many attempts have been adopted to improve their radiation enhancement effect through regulation of their size, shape, and/or surface chemistry, few methods have achieved satisfactory radiotherapeutic outcomes. Herein, we propose a sequential drug treatment strategy through cell cycle regulation for achieving improved radiotherapeutic performance of the nanoradiosensitizers.

A Photo-triggered and photo-calibrated nitric oxide donor: Rational design, spectral characterizations, and biological applications.

Nitric oxide (NO) donors are valuable tools to probe the profound implications of NO in health and disease. The elusive nature of NO bio-relevance has largely limited the use of spontaneous NO donors and promoted the development of next generation NO donors, whose NO release is not only stimulated by a trigger, but also readily monitored via a judiciously built-in self-calibration mechanism. Light is without a doubt the most sensitive, versatile and biocompatible method of choice for both triggering and monitoring, for applications in complex biological matrices.

Impact of Menopause on Quality of Life in Community-based Women in China: 1 Year Follow-up.

Quality of life (QOL) throughout menopause has become an outcome variable requiring measurement in clinical care. Staff nurses can provide earlier nursing during the menopausal transition (MT) stage. The purpose of this study was to describe the changes of QOL in different stages of the MT according to The Stages of Reproductive Aging Workshop (STRAW) in Chinese women in community settings.

A Water-Soluble, Green-Light Triggered, and Photo-Calibrated Nitric Oxide Donor for Biological Applications.

Nitric oxide (NO) is a versatile endogenous molecule, involved in various physiological processes and implicated in the progression of many pathological conditions. Therefore, NO donors are valuable tools in NO related basic and applied applications. The traditional spontaneous NO donors are limited in scenarios where flux, localization, and dose of NO could be monitored.

One-Step Synthesis of Ultrasmall and Ultrabright Organosilica Nanodots with 100% Photoluminescence Quantum Yield: Long-Term Lysosome Imaging in Living, Fixed, and Permeabilized Cells.

Water-dispersible nanomaterials with superbright photoluminescence (PL) emissions and narrow PL bandwidths are urgently desired for various imaging applications. Herein, for the first time, we prepared ultrasmall organosilica nanodots (OSiNDs) with an average size of ∼2.0 nm and ∼100% green-emitting PL quantum efficiency via a one-step hydrothermal treatment of two commercial reagents (a silane molecule and rose bengal).

Permeabilization-Tolerant Plasma Membrane Imaging Reagent Based on Amine-Rich Glycol Chitosan Derivatives.

Immunofluorescence staining is a crucial tool for studying the structure and behavior of intracellular proteins and organelles. During the staining process, the permeabilization treatment is usually required to enhance the penetration of a fluorescent antibody into the cells. However, since most of the membrane imaging dyes as well as the membrane lipids will detach from the cell surface after permeabilization, membrane labeling using these dyes is not compatible with immunofluorescence staining.

Plasma membrane activatable polymeric nanotheranostics with self-enhanced light-triggered photosensitizer cellular influx for photodynamic cancer therapy.

To address the issue of low cellular uptake of photosensitizers by cancer cells in photodynamic therapy (PDT), we designed a smart plasma membrane-activatable polymeric nanodrug by conjugating the photosensitizer protoporphyrin IX (PpIX) and polyethylene glycol (PEG) with glycol chitosan (GC). The as-prepared GC-PEG-PpIX can self-assemble into core-shell nanoparticles (NPs) in aqueous solution and the fluorescence of PpIX moieties in the inner core is highly quenched due to strong π-π stacking. Interestingly, when encountering plasma membranes, the GC-PEG-PpIX NPs can disassemble and stably attach to plasma membranes due to the membrane affinity of PpIX moieties, which effectively suppresses the self-quenching of PpIX, leading to significantly enhanced fluorescence and singlet oxygen (O) production upon laser irradiation.

Shape-Dependent Radiosensitization Effect of Gold Nanostructures in Cancer Radiotherapy: Comparison of Gold Nanoparticles, Nanospikes, and Nanorods.

The shape effect of gold (Au) nanomaterials on the efficiency of cancer radiotherapy has not been fully elucidated. To address this issue, Au nanomaterials with different shapes but similar average size (∼50 nm) including spherical gold nanoparticles (GNPs), gold nanospikes (GNSs), and gold nanorods (GNRs) were synthesized and functionalized with poly(ethylene glycol) (PEG) molecules. Although all of these Au nanostructures were coated with the same PEG molecules, their cellular uptake behavior differed significantly.

Bacteria-derived fluorescent carbon dots for microbial live/dead differentiation.

Microbial viability assessment plays a key role in many areas such as pathogen detection, infectious disease treatment and antimicrobial drug development. Many conventional viability dyes (such as propidium iodide, PI) used for differentiating live/dead microbes suffer from notable cytotoxicity, poor photostability and are of high cost. Thus their applications for accurate microbial viability determination are limited.

Subcellular Fate of a Fluorescent Cholesterol-Poly(ethylene glycol) Conjugate: An Excellent Plasma Membrane Imaging Reagent.

Cholesterol-containing molecules or nanoparticles play a significant role in achieving favorable plasma membrane imaging and efficient cellular uptake of drugs by the excellent membrane anchoring capability of the cholesterol moiety. By linking cholesterol to a water-soluble component (such as poly(ethylene glycol), PEG), the resulting cholesterol-PEG conjugate can form micelles in aqueous solution through self-assembly, and such a micellar structure represents an important drug delivery vehicle in which hydrophobic drugs can be encapsulated. However, the understanding of the subcellular fate and cytotoxicity of cholesterol-PEG conjugates themselves remains elusive.

Universal Cell Surface Imaging for Mammalian, Fungal, and Bacterial Cells.

Because of the distinct surface structures of different cells (mammalian cells, fungi, and bacteria), surface labeling for these cells requires a variety of fluorescent dyes. Besides, fluorescent dyes (especially the commercial ones) for staining Gram-negative bacterial cell walls are still lacking. Herein, a conformation-adjustable glycol chitosan (GC) derivative (GC-PEG cholesterol-FITC) with "all-in-one" property was developed to realize universal imaging for plasma membranes of mammalian cells (via hydrophobic interaction) and cell walls of fungal and bacterial cells (via electrostatic interaction).

Enhanced cell membrane enrichment and subsequent cellular internalization of quantum dots via cell surface engineering: illuminating plasma membranes with quantum dots.

Efficient cellular uptake of nanoparticles is crucial for modulating the cell behaviors as well as dictating the cell fate. In this work, by using two commercial reagents (the membrane modification reagent "cholesterol-PEG-biotin" and the avidin-modified quantum dots (QDs) "QD-avidin"), we achieved the enhanced plasma membrane enrichment and endocytosis of fluorescent QDs in cancer cells through cell surface engineering. The QD-cell interaction involved two stages: adsorption and internalization.

Long-Time Plasma Membrane Imaging Based on a Two-Step Synergistic Cell Surface Modification Strategy.

Long-time stable plasma membrane imaging is difficult due to the fast cellular internalization of fluorescent dyes and the quick detachment of the dyes from the membrane. In this study, we developed a two-step synergistic cell surface modification and labeling strategy to realize long-time plasma membrane imaging. Initially, a multisite plasma membrane anchoring reagent, glycol chitosan-10% PEG2000 cholesterol-10% biotin (abbreviated as "GC-Chol-Biotin"), was incubated with cells to modify the plasma membranes with biotin groups with the assistance of the membrane anchoring ability of cholesterol moieties.

Imaging plasma membranes without cellular internalization: multisite membrane anchoring reagents based on glycol chitosan derivatives.

Plasma membrane imaging has received substantial attention due to its capability for dynamically tracing significant biological processes including cell trafficking, vesicle transportation, apoptosis, etc. However, cellular internalization of staining molecules poses challenges to the development of fluorescent dyes to specifically label plasma membranes rather than intracellular organelles. In this work, glycol chitosan, a multifunctional biomaterial derived from natural polymers, was used for the first time to image the plasma membranes based on a strategy of multisite membrane anchoring.