Correlation of [RuCl3(dppb)(VPy)] cytotoxicity with its effects on the cell membranes: an investigation using Langmuir monolayers as membrane models.

One of the major challenges in drug design is to identify compounds with potential toxicity toward target cells, preferably with molecular-level understanding of their mode of action. In this study, the antitumor property of a ruthenium complex, mer-[RuCl3(dppb)(VPy)] (dppb = 1,4-bis(diphenylphosphine)butane and VPy = 4-vinylpyridine) (RuVPy), was analyzed. Results showed that this compound led to a mortality rate of 50% of HEp-2 cell with 120 ± 10 µmol L(-1), indicating its high toxicity. Then, to prove if its mode of action is associated with its interaction with cell membranes, Langmuir monolayers were used as a membrane model. RuVPy had a strong effect on the surface pressure isotherms, especially on the elastic properties of both the zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) phospholipids. These data were confirmed by polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). In addition, interactions between the positive group from RuVPy and the phosphate group from the phospholipids were corroborated by density functional theory (DFT) calculations, allowing the determination of the Ru complex orientation at the air-water interface. Although possible contributions from receptors or other cell components cannot be discarded, the results reported here represent evidence for significant effects on the cell membranes which are probably associated with the high toxicity of RuVPy.

An intraocular dye solution based on lutein and zeaxanthin in a surrogate internal limiting membrane model: a Langmuir monolayer study.

Investigating the role of biomolecules and bioactive molecules associated with membranes is fundamental to comprehend at the molecular point-of-view biochemical and clinical processes that occur at biointerfaces. In this paper we exploit the interaction of an intraocular dye solution based on lutein and zeaxanthin in surrogate internal limiting membrane (ILM) models, consisting of dipalmitoyphosphatidylcholine (DPPC) Langmuir monolayers, pure or mixed with collagen, proteoglycan and laminin. The interactions between the film components occurring at the air-water interface were investigated with surface pressure-area isotherms and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS). A natural dye solution based on lutein and zeaxanthin, employed to label ILM in ophthalmic surgery, was incorporated in the ILM model, and the data suggested non-rupture of the structure of the membrane, with predominance of interactions based on intermolecular forces.

Comparative study of liponucleosides in Langmuir monolayers as cell membrane models.

Liponucleosides may assist the anchoring of nucleic acid nitrogen bases into biological membranes for tailored nanobiotechnological applications. To this end precise knowledge about the biophysical and chemical details at the membrane surface is required. In this paper, we used Langmuir monolayers as simplified cell membrane models and studied the insertion of five lipidated nucleosides. These molecules varied in the type of the covalently attached lipid group, the nucleobase, and the number of hydrophobic moieties attached to the nucleoside. All five lipidated nucleosides were found to be surface-active and capable of forming stable monolayers. They could also be incorporated into dipalmitoylphosphatidylcholine (DPPC) monolayers, four of which induced expansion in the surface pressure isotherm and a decrease in the surface compression modulus of DPPC. In contrast, one nucleoside possessing three alkyl chain modifications formed very condensed monolayers and induced film condensation and an increase in the compression modulus for the DPPC monolayer, thus reflecting the importance of the ability of the nucleoside molecules to be arranged in a closely packed manner. The implications of these results lie on the possibility of tuning nucleic acid pairing by modifying structural characteristics of the liponucleosides.

Interaction of oligonucleotide-based amphiphilic block copolymers with cell membrane models.

Oligonucleotides have unique molecular recognition properties, being involved in biological mechanisms such as cell-surface receptor recognition or gene silencing. For their use in human therapy for drug or gene delivery, the cell membrane remains a barrier, but this can be obviated by grafting a hydrophobic tail to the oligonucleotide. Here we demonstrate that two oligonucleotides, one consisting of 12 guanosine units (G(12)), and the other one consisting of five adenosine and seven guanosine (A(5)G(7)) units, when functionalized with poly(butadiene), namely PB-G(12) and PB-A(5)G(7), can be inserted into Langmuir monolayers of dipalmitoyl phosphatidyl choline (DPPC), which served as a cell membrane model. PB-G(12) and PB-A(5)G(7) were found to affect the DPPC monolayer even at high surface pressures. The effects from PB-G(12) were consistently stronger, particularly in reducing the elasticity of the DPPC monolayers, which may have important biological implications. Multilayers of DPPC and nucleotide-based copolymers could be adsorbed onto solid supports, in the form of Y-type LB films, in which the molecular-level interaction led to lower energies in the vibrational spectra of the nucleotide-based copolymers. This successful deposition of solid films opens the way for devices to be produced which exploit the molecular recognition properties of the nucleotides.

Properties of lipophilic nucleoside monolayers at the air-water interface.

The capability of self-assembly and molecular recognition of biomolecules is essential for many nanotechnological applications, as in the use of alkyl-modified nucleosides and oligonucleotides to increase the cellular uptake of DNA and RNA. In this study, we show that a lipophilic nucleoside, which is an isomer mixture of 2'-palmitoyluridin und 3'-palmitoyluridin, forms Langmuir monolayers and Langmuir-Blodgett films as a typical amphiphile, though with a smaller elasticity. The nucleoside may be incorporated into dipalmitoyl phosphatidyl choline (DPPC) monolayers that serve as a simplified cell membrane model. The molecular-level interactions between the nucleoside and DPPC led to a remarkable condensation of the mixed monolayer, which affected both surface pressure and surface potential isotherms. The morphology of the mixed monolayers was dominated by the small domains of the nucleoside. The mixed monolayers could be deposited onto solid substrates as a one-layer Langmuir Blodgett film that displayed UV-vis absorption spectra typical of aggregated nucleosides owing to the interaction between the nucleoside and DPPC. The formation of solid films with DNA building blocks in the polar heads may open the way for devices and sensors be produced to exploit their molecular recognition properties.