Lipid Giant Vesicles Engulf Living Bacteria Triggered by Minor Enhancement in Membrane Fluidity.

Antibacterial amphiphiles normally kill bacteria by destroying the bacterial membrane. Whether and how antibacterial amphiphiles alter normal cell membrane and lead to subsequent effects on pathogen invasion into cells have been scarcely promulgated. Herein, by taking four antibacterial gemini amphiphiles with different spacer groups to modulate cell-mimic phospholipid giant unilamellar vesicles (GUVs), bacteria adhesion on the modified GUVs surface and bacteria engulfment process by the GUVs are clearly captured by confocal laser scanning microscopy. Further characterization shows that the enhanced cationic surface charge of GUVs by the amphiphiles determines the bacteria adhesion amount, while the involvement of amphiphile in GUVs results in looser molecular arrangement and concomitant higher fluidity in the bilayer membranes, facilitating the bacteria intruding into GUVs. This study sheds new light on the effect of amphiphiles on membrane bilayer and the concurrent effect on pathogen invasion into cell mimics and broadens the nonprotein-mediated endocytosis pathway for live bacteria.

A Polyaromatic Gemini Amphiphile That Assembles into a Well-Defined Aromatic Micelle with Higher Stability and Host Functions.

A gemini-type amphiphilic molecule, constituted of two V-shaped polyaromatic amphiphiles linked by a linear acetylene spacer, was synthesized. The gemini amphiphile assembles into a well-defined aromatic micelle (ca. 2 nm in core diameter), providing higher stability in water even at low concentration (0.09 mm) and high temperature (>130 °C). Unlike common gemini amphiphiles with aliphatic chains, the present amphiphile and its micellar assembly emit green and orange fluorescence (ΦF =33 and 9 %), respectively. Despite strong and multiple π-stacks of the polyaromatic panels of the amphiphiles, the water-soluble gemini aromatic micelle incorporates medium-size to large hydrophobic compounds into the frameworks. Interestingly, the guest binding capability toward large planar molecules was enhanced by more than two times through the pre-encapsulation of spherical molecules in the cavity.

Reversing the Trend: Deciphering Self-Assembly of Unconventional Amphiphiles Having Both Alkyl-Chain and PEG.

In the field of molecular self-assembly, the core of an assembly is always made up of hydrophobic moiety like a long alkyl chain, whereas the outer part has always been a hydrophilic moiety such as poly(ethylene glycol) (PEG), or charged species. Hence, reversing the trend to manifest self-assembled structures with a PEG core and a surface consisting of alkyl chains in aqueous system is incredibly challenging. Herein, we architected a unique class of cationic bolaamphiphiles containing low molecular weight PEG and alkyl chains of different lengths. The bolaamphiphiles spontaneously form vesicles without external stimuli. These vesicles are unprecedented because PEG makes up the vesicle core, while the alkyl chains appear on the vesicles' exterior. Hence, this particular design reverses the usual trend of self-assembly formation. The vesicle size increases with the increase in alkyl chain-length. To our great surprise, we obtained large micelles for longest alkyl-chain amphiphile, which in turn act as a gemini amphiphile. The shift from a particular bolaamphiphile to gemini amphiphile with the variation of alkyl chain is also unexplored. Therefore, this specific class of self-assembled structure would compound a new paradigm in molecular self-assembly and supramolecular chemistry.

Transport of cationic liposomes in a human blood brain barrier model: Role of the stereochemistry of the gemini amphiphile on liposome biological features.

HYPOTHESIS: The positive charge on liposome surface is known to promote the crossing of the Blood brain barrier (BBB). However, when diastereomeric cationic gemini amphiphiles are among lipid membrane components, also the stereochemistry may affect the permeability of the vesicle across the BBB. EXPERIMENTS: Liposomes featuring cationic diasteromeric gemini amphiphiles were formulated, characterized, and their interaction with cell culture models of BBB investigated. FINDINGS: Liposomes featuring the gemini amphiphiles were internalized in a monolayer of brain microvascular endothelial cells derived from human induced pluripotent stem cells (hiPSC) through an energy dependent transport, internalization involving both clathrin- and caveolae-mediated endocytosis. On the same formulations, the permeability was also evaluated across a human derived in vitro BBB transport model. The permeability of liposomes featuring the gemini amphiphiles was significantly higher compared to that of neutral liposomes (DPPC/Cholesterol), that were not able to cross BBB. Most importantly, the permeability was influenced by the stereochemistry of the gemini and pegylation of these formulations did not result in a drastic reduction of the crossing ability. The in vitro iPSC-derived BBB models used in this work represent an important advancement in the drug discovery research of novel brain delivery strategies and therapeutics for central nervous system diseases.

Gemini Thermotropic Smectic Liquid Crystals for Two-Dimensional Nanostructured Water-Treatment Membranes.

We have developed a two-dimensional (2D) liquid-crystalline (LC) nanostructured water-treatment membrane showing high virus rejection ability (over 99.99997% for bacteriophage Qß) and improved water permeation. Polymerizable gemini amphiphiles have been designed and synthesized. They have H-shaped gemini-type structures of thermotropic smectic liquid crystals composed of cationic imidazolium moieties. One of the gemini amphiphiles shows a smectic A phase with an interdigitated bilayer structure. A cross-linked self-standing 2D nanostructured polymer film has been obtained by in situ photopolymerization of the gemini amphiphile in the smectic phase. The length of linkers in gemini amphiphiles affects the formation of LC phases. The 2D nanostructured membrane also showed selective salt rejection.

Influence of lipid composition on the ability of liposome loaded voacamine to improve the reversion of doxorubicin resistant osteosarcoma cells.

The plant alkaloid voacamine (VOA) displays many interesting pharmacological activities thus, considering its scarce solubility in water, its encapsulation into liposome formulations for its delivery is an important goal. Different cationic liposome formulations containing a phospholipid, cholesterol and one of two diasteromeric cationic surfactants resulted able to maintain a stable transmembrane difference in ammonium sulfate concentration and/or pH gradient and to accumulate VOA in their internal aqueous bulk. The fluidity of the lipid bilayer affects both the ability to maintain a stable imbalance of protons and/or ammonium ions across the membrane and the entrapment efficiency. It was shown that VOA loaded into liposomes is more efficient than the free alkaloid to revert resistance of osteosarcoma cells resistant to doxorubicin to an extent depending on their composition.