Understanding the Interaction of Pluronics L61 and L64 with a DOPC Lipid Bilayer: An Atomistic Molecular Dynamics Study

We investigate the interactions of Pluronics L61 and L64 with a dioleylphosphatidylcholine (DOPC) lipid bilayer by atomistic molecular dynamics simulations using the all-atom OPLS force field. Our results show that the initial configuration of the polymer with respect to the bilayer determines its final conformation within the bilayer. When the polymer is initially placed at the lipid/water interface, we observe partial insertion of the polymer in a U-shaped conformation. On the other hand, when the polymer is centered at the bilayer, it stabilizes to a transmembrane state, which facilitates water transport across the bilayer. We show that membrane thickness decreases while its fluidity increases in the presence of Pluronics. When the polymer concentration inside the bilayer is high, pore formation is initiated with L64. Our results show good agreement with existing experimental data and reveal that the hydrophilic/lipophilic balance of the polymer plays a critical role in the interaction mechanisms as well as in the dynamics of Pluronics with and within the bilayer

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Release Rates of Liposomal Contents Are Controlled by Kosmotropes and Chaotropes

Contents release from redox-responsive liposomes is anion specific. Liposomal contents release is initiated by contact of apposed liposome bilayers having in their outer leaflet 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), whose presence is due to redox-stimulated removal of a quinone propionic acid protecting group (Q) from Q-DOPE lipids. Contents release occurs upon the phase transition of DOPE from its lamellar liquid crystalline (L(α)) to hexagonal-II inverted micelle (H(II)) phase. Contents release is slower in the presence of weakly hydrated chaotropic anions versus highly hydrated kosmotropic anions and is attributed to ion accumulation near the zwitterionic DOPE head groups, in turn altering head group hydration, as indicated by the L(α)→H(II) phase transition temperature, T(H), for DOPE. The results are significant, not only for mechanistic aspects of liposome contents release in DOPE-based systems, but also for drug delivery applications wherein exist at drug targeting sites variations in type and concentration of ions and neutral species