The multiple faces of self-assembled lipidic systems

Lipids, the building blocks of cells, common to every living organisms, have the propensity to self-assemble into well-defined structures over short and long-range spatial scales. The driving forces have their roots mainly in the hydrophobic effect and electrostatic interactions. Membranes in lamellar phase are ubiquitous in cellular compartments and can phase-separate upon mixing lipids in different liquid-crystalline states. Hexagonal phases and especially cubic phases can be synthesized and observed in vivo as well. Membrane often closes up into a vesicle whose shape is determined by the interplay of curvature, area difference elasticity and line tension energies, and can adopt the form of a sphere, a tube, a prolate, a starfish and many more. Complexes made of lipids and polyelectrolytes or inorganic materials exhibit a rich diversity of structural morphologies due to additional interactions which become increasingly hard to track without the aid of suitable computer models. From the plasma membrane of archaebacteria to gene delivery, self-assembled lipidic systems have left their mark in cell biology and nanobiotechnology; however, the underlying physics is yet to be fully unraveled

Cationic liposome–nucleic acid complexes: liquid crystal phases with applications in gene therapy

Cationic liposome (CL) carriers of nucleic acids are primarily studied because of their applications in gene delivery and gene silencing with CL-DNA and CL-siRNA (short-interfering RNA) complexes, respectively, and their implications to ongoing clinical gene therapy trials worldwide. A series of synchrotron-based small-angle-x-ray scattering studies, dating back to 1997, has revealed that CL-nucleic acid complexes spontaneously assemble into distinct novel liquid crystalline phases of matter. Significantly, transfection efficiency (TE; a measure of expression of an exogenous gene that is transferred into the cell by the lipid carrier) has been found to be dependent on the liquid crystalline structure of complexes, with lamellar complexes showing strong dependence on membrane charge density (σ(M)) and non-lamellar complexes exhibiting TE behavior independent ofσ(M). The review describes our current understanding of the structures of different liquid crystalline CL-nucleic acid complexes including the recently described gyroid cubic phase of CL-siRNA complexes used in gene silencing. It further makes apparent that the long-term goal of developing optimized liquid crystalline CL-nucleic acid complexes for successful medical applications requires a comprehensive understanding of the nature of the interactions of distinctly structured complexes with cell membranes and events leading to release of active nucleic acids within the cell cytoplasm

MACROLATTICE FORMATION IN AMORPHOUS ASSOCIATING POLYMERS

We report on high-resolution synchrotron x-ray scattering studies of melts of a series of linear polyisoprenes with highly polar sulfozwitterion groups at one end. Studies were carried out for six different molecular weights between 2200 and 28 000. For low molecular weights between 2200 and 4650, we observe a lattice with the symmetry of a triangular array of cylinders. The lattice ordering is strong; the nominal domain size exceeds 5000 angstrom. A structural phase transition to a cubic (bcc) lattice with long-range order is observed to occur for melts with molecular weights between 4650 and 14 000. The lattice spacing increases over the molecular range between 83 angstrom (for M(w) = 2200) and 224 angstrom (for M(w) = 28 000). In contrast to usual block copolymers, for these copolymers the long-range order sets in at extremely small volume fraction of ionic species, less than 1%

Paclitaxel suppresses Tau-mediated microtubule bundling in a concentration-dependent manner.

Background: Microtubules (MTs) are protein nanotubes comprised of straight protofilaments (PFs), head to tail assemblies of alpha beta-tubulin heterodimers. Previously, it was shown that Tau, a microtubule-associated protein (MAP) localized to neuronal axons, regulates the average number of PFs in microtubules with increasing inner radius observed for increasing Tau/tubulin-dimer molar ratio Phi(Tau) at paclitaxel/tubulin-dimer molar ratio Lambda(ptxl) = 1/1. Methods: We report a synchrotron SAXS and TEM study of the phase behavior of microtubules as a function of varying concentrations of paclitaxel (1/32 <= Lambda(ptxl) <= 1/4) and Tau (human isoform 3RS, 0 <= Phi(3Rs) <= 1/2) at room temperature. Results: Tau and paclitaxel have opposing regulatory effects on microtubule bundling architectures and microtubule diameter. Surprisingly and in contrast to previous results at Air = 1/1 where microtubule bundles are absent, in the lower paclitaxel concentration regime (Lambda(ptxl) <= 1/4), we observe both microtubule doublets and triplets with increasing Tau. Furthermore, increasing paditaxel concentration (up to Lambda(ptxl) = 1/1) slightly decreased the average microtubule diameter (by similar to 1 PF) while increasing Tau concentration (up to Phi(3RS) = 1/2) significantly increased the diameter (by similar to 2-3 PFs). Conclusions: The suppression of Tau-mediated microtubule bundling with increasing paclitaxel is consistent with paditaxel seeding more, but shorter, microtubules by rapidly exhausting tubulin available for polymerization. Microtubule bundles require the aggregate Tau-Tau attractions along the microtubule length to overcome individual microtubule thermal energies disrupting bundles. General significance: Investigating MAP-mediated interactions between microtubules (as it relates to in vivo behavior) requires the elimination or minimization of paclitaxel. (C) 2016 Elsevier B.V. All rights reserved

Liquid crystal assemblies in biologically inspired systems

In this paper, which is part of a collection in honor of Noel Clark's remarkable career on liquid crystal and soft matter research, we present examples of biologically inspired systems, which form liquid crystal (LC) phases with their LC nature impacting biological function in cells or being important in biomedical applications. One area focuses on understanding network and bundle formation of cytoskeletal polyampholytes (filamentous-actin, microtubules, and neurofilaments). Here, we describe studies on neurofilaments (NFs), the intermediate filaments of neurons, which form open network nematic liquid crystal hydrogels in axons. Synchrotron small-angle-x-ray scattering studies of NF-protein dilution experiments and NF hydrogels subjected to osmotic stress show that neurofilament networks are stabilized by competing long-range repulsion and attractions mediated by the neurofilament's polyampholytic sidearms. The attractions are present both at very large interfilament spacings, in the weak sidearm-interpenetrating regime, and at smaller interfilament spacings, in the strong sidearm-interpenetrating regime. A second series of experiments will describe the structure and properties of cationic liposomes (CLs) complexed with nucleic acids (NAs). CL-NA complexes form liquid crystalline phases, which interact in a structure-dependent manner with cellular membranes enabling the design of complexes for efficient delivery of nucleic acid (DNA, RNA) in therapeutic applications