A segment contribution activity coefficient model, derived from the polymer nonrandom two-liquid model, is proposed for fast, qualitative estimation of the solubilities of organic nonelectrolytes in common solvents. Conceptually, the approach suggests that one account for the liquid nonideality of mixtures of complex pharmaceutical molecules and small solvent molecules in terms of interactions between three pairwise interacting conceptual segments:  hydrophobic segment, hydrophilic segment, and polar segment. In practice, these conceptual segments become the molecular descriptors used to represent the molecular surface characteristics of each solute and solvent molecule. The treatment results in component-specific molecular parameters:  hydrophobicity X, polarity Y, and hydrophilicity Z. Once the molecular parameters are identified from experimental data for common solvents and solute molecules, the model offers a simple and practical thermodynamic framework to estimate solubilities and to perform other phase equilibrium calculations in support of pharmaceutical process design.

A generalized electrolyte Non-Random Two-Liquid (eNRTL)

Layer-by-layer assembly of polyelectrolyte multilayer (PEM) films represents a bottom-up approach for re-engineering the molecular landscape of cell surfaces with spatially continuous and molecularly uniform ultrathin films. However, fabricating PEMs on viable cells has proven challenging owing to the high cytotoxicity of polycations. Here, we report the rational engineering of a new class of PEMs with modular biological functionality and tunable physicochemical properties which have been engineered to abrogate cytotoxicity. Specifically, we have discovered a subset of cationic copolymers that undergoes a conformational change, which mitigates membrane disruption and facilitates the deposition of PEMs on cell surfaces that are tailorable in composition, reactivity, thickness, and mechanical properties. Furthermore, we demonstrate the first successful in vivo application of PEM-engineered cells, which maintained viability and function upon transplantation and were used as carriers for in vivo delivery of PEMs containing biomolecular payloads. This new class of polymeric film and the design strategies developed herein establish an enabling technology for cell transplantation and other therapies based on engineered cells.

Self-assembling peptides have been previously designed that assemble into macroscopic membranes, nanotapes, and filaments through electrostatic interactions. However, the formation of highly ordered collagen-like fibrils, which display D-periodic features, has yet to be achieved. In this report, we describe for the first time a synthetic peptide system that self-assembles into a fibrous structure with well-defined periodicity that can be visualized by transmission electron microscopy (TEM). Specifically, we designed and synthesized a peptide that utilizes charged amino acids within the ubiquitous Xaa-Yaa-Gly triad sequence to bias the self-assembly into collagen-like homotrimeric helices that are capable of fibrillogenesis with the production of D-periodic microfibers. Potential molecular mechanisms for peptide assembly into triple-helical protomers and their subsequent organization into structurally defined, linear assemblies were explored through molecular dynamics (MD) simulations. The formation of thermodynamically stable complexes was attributed to the presence of strong electrostatic and hydrogen bond interactions at staggered positions along the linear assembly. This unexpected mimicry of native collagen structure using a relatively simple oligopeptide sequence establishes new opportunities for engineering linear assemblies with highly ordered nano- and microscale periodic features. In turn, the capacity to precisely design periodic elements into an assembly that faithfully reproduces these features over large length scales may facilitate the fabrication of ordered two- and three-dimensional fiber networks containing oriented biologically, chemically, or optically active elements.

No abstract

Differences of ionic concentrations across lipid bilayers are some of the primary energetic driving forces for cellular electrophysiology. While macroscopic models of asymmetric ionic solutions are well-developed, their connection to ion, water, and lipid interactions at the atomic scale are much more poorly understood. In this study, we used molecular dynamics to examine a system of two chambers of equal ionic strength, but differing amounts of NaCl and KCl, separated by a lipid bilayer. Our expectation was that the net electrostatic potential difference between the two chambers should be small or zero. Contrary to our expectation, a large potential difference (-70 mV) slowly evolved across the two water chambers over the course of our 172-ns simulation. This potential primarily originated from strong Na(+) binding to the carbonyls of the phosphatidylcholine lipids. This ion adsorption also led to significant structural and mechanical changes in the lipid bilayer. We discuss this surprising result in the context of indirect experimental evidence for Na(+) interaction with bilayers as well as potential caveats in current biomembrane simulation methodology, including force-field parameters and finite size effects.

In addition to the pathway end products, campesterol, sitosterol, and stigmasterol, some biosynthetic intermediates such as cycloartenol also accumulated in transgenic tissues. Most of the overproduced sterols were detected as steryl-esters and were likely to be stored in cytoplasmic lipid bodies. These data strongly support the conclusion that plant HMCR is a key limiting enzyme in phytosterol biosynthesis.

The electrolyte nonrandom two-liquid (eNRTL) model is reformulated as a symmetric activity coefficient model with the reference states chosen to be pure liquids for solvents and pure fused salts for electrolytes. These reference states are consistently used in the local interaction term, represented by a reformulated NRTL expression, and the long-range interaction term, represented by an extended symmetric Pitzer−Debye−Hückel expression. Retaining the local electroneutrality and like-ion repulsion hypotheses, the new symmetric electrolyte NRTL model yields simpler activity coefficient expressions for both molecular and ionic species. The utility of the model is demonstrated with vapor−liquid equilibrium, liquid−liquid equilibrium, and solid−liquid equilibria of several mixed solvent electrolyte systems.