A constitutional isomeric library synthesized by a modular approach has been used to discover six amphiphilic Janus dendrimer primary structures, which self-assemble into uniform onion-like vesicles with predictable dimensions and number of internal bilayers. These vesicles, denoted onion-like dendrimersomes, are assembled by simple injection of a solution of Janus dendrimer in a water-miscible solvent into water or buffer. These dendrimersomes provide mimics of double-bilayer and multibilayer biological membranes with dimensions and number of bilayers predicted by the Janus compound concentration in water. The simple injection method of preparation is accessible without any special equipment, generating uniform vesicles, and thus provides a promising tool for fundamental studies as well as technological applications in nanomedicine and other fields.synthetic membranes | biomembrane mimics | multibilayer vesicles M ost living organisms contain single-bilayer membranes composed of lipids, glycolipids, cholesterol, transmembrane proteins, and glycoproteins (1). Gram-negative bacteria (2, 3) and the cell nucleus (4), however, exhibit a strikingly special envelope that consists of a concentric double-bilayer membrane. More complex membranes are also encountered in cells and their various organelles, such as multivesicular structures of eukaryotic cells (5) and endosomes (6), and multibilayer structures of endoplasmic reticulum (7,8), myelin (9, 10), and multilamellar bodies (11,12). This diversity of biological membranes inspired corresponding biological mimics. Liposomes ( Fig. 1) self-assembled from phospholipids are the first mimics of singlebilayer biological membranes (13-16), but they are polydisperse, unstable, and permeable (14). Stealth liposomes coassembled from phospholipids, cholesterol, and phospholipids conjugated with poly(ethylene glycol) exhibit improved stability, permeability, and mechanical properties (17)(18)(19)(20). Polymersomes (21-24) assembled from amphiphilic block copolymers exhibit better mechanical properties and permeability, but are not always biocompatible and are polydisperse. Dendrimersomes (25-28) self-assembled from amphiphilic Janus dendrimers and minidendrimers (26-28) have also been elaborated to mimic single-bilayer biological membranes. Amphiphilic Janus dendrimers take advantage of multivalency both in their hydrophobic and hydrophilic parts (23,(29)(30)(31)(32). Dendrimersomes are assembled by simple injection (33) of a solution of an amphiphilic Janus dendrimer (26) in a water-soluble solvent into water or buffer and produce uniform (34), impermeable, and stable vesicles with excellent mechanical properties. In addition, their size and properties can be predicted by their primary structure (27). Amphiphilic Janus glycodendrimers self-assemble into glycodendrimersomes that mimic the glycan ligands of biological membranes (35). They have been demonstrated to be bioactive toward biomedically relevant bacterial, plant, and human lectins, and could have numerous applications i...

An accelerated modular synthesis of six libraries containing 29 amphiphilic Janus dendrimers, employed to discover and predict functions via primary structures, is reported. These dendrimers were constructed from a single hydrophobic and a single hydrophilic dendron, interconnected with l-Ala to form two constitutional isomeric libraries, with Gly to produce one library, and with l-propanediol ester to generate two additional constitutional isomeric libraries. They are denoted "single-single" amphiphilic Janus dendrimers. Assemblies obtained by injection of their ethanol solution into water were analyzed by dynamic light scattering and cryogenic transmission electron microscopy. A diversity of complex structures including soft and hard dendrimersomes, cubosomes, solid lamellae, and rod-like micelles were obtained in water. It was discovered that the "single-single" amphiphilic Janus dendrimers containing three triethylene glycol groups in the hydrophilic dendron favored the formation of dendrimersomes. Assemblies in bulk analyzed by differential scanning calorimetry and powder X-ray diffraction revealed that the amphiphilic Janus dendrimers with melting point or glass transition below room temperature self-assemble into soft dendrimersomes in water, while those with higher temperature transitions produce hard assemblies. In the range of concentrations where their size distribution is narrow, the diameter of the dendrimersomes is predictable by the d-spacing of their assemblies in bulk. These results suggested the synthesis of Library 6 containing two simpler constitutional isomeric benzyl ester based amphiphilic Janus dendrimers that self-assemble in water into soft dendrimersomes and multidendrimersome dendrimersomes with predictable dimensions.

Glycodendrimersomes with programmable surface display of glycan, together with artificially engineered galectins, were used to understand the physiological significance of human lectins with homodimeric and tandem-repeat-type displays. The mode of topological surface presentation and the density of glycan affected vesicle aggregation mediated by multivalent carbohydrate-protein interactions. The cross-linking capacity of homodimeric lectins was enhanced by covalent connection of the two carbohydrate-binding sites. These findings highlight the value of glycodendrimersomes as versatile cell membrane mimetics, and assays provide diagnostic tools for protein functionality. This work also provides guidelines for the design of cell separators, bioactive matrices, bioeffectors, and other biomedical applications.

The extended Canadian Middle Atmosphere Model (eCMAM) was recently run in a nudged mode using reanalysis data from the ground to 1 hPa for the period of January 1979 to June 2010 (hence the name eCMAM30). In this paper, eCMAM30 temperature is used to examine the background mean temperature, the spectrum of the diurnal tides, and the climatology of the migrating diurnal tide Dw1 and three nonmigrating diurnal tides De3, Dw2, and Ds0 in the stratosphere, mesosphere, and lower thermosphere. The model results are then compared to the diurnal tidal climatology derived from Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) observations between 40 to 110 km and 50°S to 50°N from January 2002 to December 2013. The model reproduces the latitudinal background mean temperature gradients well except that the cold mesopause temperature in eCMAM30 is 10 to 20 K colder than SABER. The diurnal tidal spectra and their relative strengths compare very well between eCMAM30 and SABER. The altitude-latitude structures for the four diurnal tidal components (Dw1, De3, Dw2, and Ds0) from the two datasets are also in very good agreement even for structures in the stratosphere with a weaker amplitude. The largest discrepancy between the model and SABER is associated with the seasonal variation of De3. In addition to the Northern Hemisphere (NH) summer maximum, a secondary maximum occurs during NH winter (December-February) in the model but is absent in SABER. The seasonal variations of the other three diurnal tidal components are in good agreement. Interannual time series of Dw1 and De3 from both eCMAM30 and SABER reveal variability with a period of 25 to 26 months, which indicates the modulation of the diurnal tides by the stratospheric quasi-biennial oscillation (QBO).

Estimates of trends in planetary boundary layer height over Europe are presented, based on daily radiosonde observations at 25 stations during 1973-2010 and using a bulk Richardson number approach to determine heights. Most stations show statistically significant increases in daytime heights in all four seasons, but fewer show statistically significant trends in nighttime heights. Daytime height variations show an expected strong negative correlation with surface relative humidity and strong positive correlation with surface temperature at most stations studied, on both year-to-year and day-to-day time scales. Similar relations hold for long-term trends: increasing daytime boundary layer height is associated with decreasing surface relative humidity and increasing surface temperature at most stations. The extent to which these changes are regionally representative or local reflections of environmental changes near the observing stations is difficult to ascertain.