The European Physical Journal E最新文献

Paclitaxel (PTX) is a hydrophobic small-molecule cancer drug that loads into the membrane (tail) region of lipid carriers such as liposomes and micelles. The development of improved lipid-based carriers of PTX is an important objective to generate chemotherapeutics with fewer side effects. The lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) show propensity for fusion with other lipid membranes, which has led to their use in lipid vectors of nucleic acids. We hypothesized that DOPE and GMO could enhance PTX delivery to cells through a similar membrane fusion mechanism. As an important measure of drug carrier performance, we evaluated PTX solubility in cationic liposomes containing GMO or DOPE. Solubility was determined by time-dependent kinetic phase diagrams generated from direct observations of PTX crystal formation using differential-interference-contrast optical microscopy. Remarkably, PTX was much less soluble in these liposomes than in control cationic liposomes containing univalent cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), which are not fusogenic. In particular, PTX was not substantially soluble in GMO-based cationic liposomes. The fusogenicity of DOPE and GMO is related to the negative spontaneous curvature of membranes containing these lipids, which drives formation of nonlamellar self-assembled phases (inverted hexagonal or gyroid cubic). To determine whether PTX solubility is governed by lipid membrane structure or by local intermolecular interactions, we used synchrotron small-angle X-ray scattering. To increase the signal/noise ratio, we used DNA to condense the lipid formulations into lipoplex pellets. The results suggest that local intermolecular interactions are of greater importance and that the negative spontaneous curvature-inducing lipids DOPE and GMO are not suitable components of liposomal carriers for PTX delivery.

Graphical abstract

Nucleic acid-based therapies have shown enormous effectiveness as vaccines against the recent COVID19 pandemics and hold great promises in the fight of a broad spectrum of diseases ranging from viral infections to cancer up to genetically transmitted pathologies. Due to their highly degradable polyanionic nature, nucleic acids need to be packed in sophisticate delivery vehicles which compact them up, protect them from early degradation and help delivery them to the right tissue/cells. Lipid-based nanoparticles (LNP) represent, at present, the main solution for nucleic acid delivery. They are made of a mixture of lipids whose key ingredient is an ionizable cationic lipid. Indeed, the interactions between the polyanionic nucleic acids and the ionizable cationic lipids, and their pH-dependent regulation in the life cycle of the nanoparticle, from production to cargo delivery, mostly determine the effectiveness of the therapeutic approach. Notwithstanding the large improvements in the delivery efficiency of LNPs in the last two decades, it is estimated that only a small fraction of the cargo is actually delivered, stimulating further research for the design of more effective LNP formulations. A rationally driven design would profit from the knowledge of the precise molecular structure of these materials, which is however still either missing or characterized by poor spatial resolution. Computational approaches have often been used as a molecular microscope either to enrich the available experimental data and provide a molecular-level picture of the LNPs or even simulate specific processes involving the formation and/or the molecular mechanisms of action of the LNP. Here, I review the recent literature in the field.

Recently Cavagna et al. (Sci Rep 13(1): 8745, 2023) documented the swarming behaviors of laboratory-based Anopheles gambiae mosquitoes. Here key observations from this 3D-video tracking study are reproduced by a minimally structured (maximum entropy) stochastic trajectory model. The modelling shows that in contrast with midge swarms which are a form of collective behavior, unperturbed mosquito swarms are more like collections of individuals that independently circulate around a fixed location. The modelling predicts the observed response Anopheles gambiae mosquitoes in wild swarms to varying wind speeds (Butail et al. in J Med Entomol 50(3): 552–559, 2013). It is shown that this response can be attributed to shear hardening. This is because mosquitoes are found to be attracted to the centre of the swarm by an effective force that increases with increasing flight speed. Mosquitoes can therefore better resist the influence of environmental disturbances by increasing their flight speeds. This contrasts with other emergent mechanical-like properties of swarming which arise accidentally without a change in an individual’s behavior. The new results add to the growing realization that perturbations can drive swarms into more robust states.

Thermodiffusion, or Soret effect, is the physical phenomenon of matter gradients originated by the migration of chemical species induced by thermal gradients. Thermodiffusion has been widely applied in the study of colloidal suspensions. In this study, we investigate the termodiffusion behavior of low-density lipoprotein (LDL) particles, by the Soret coefficient measurement. It is a new approach to studies of plasma lipoproteins. The experimental work was based on thermal- and Soret-lens effects. These effects were induced by laser irradiation of the samples, at two different time scales, in a Z-scan setup. LDL samples were analyzed under physiological conditions, notedly, ionic strength and pH, and at different temperatures. Temperature dependence of Soret coefficient showed a slight decrease in the absolute value of this coefficient, as a function of temperature increasing. However, its sign does not change at the temperatures investigated (15, 22.5 and 37.5 °C). The results show that LDL particles exhibit thermophilic behavior. The origin of this thermophilic behavior is not yet completely understood. We discuss some aspects that can be related with the Soret effect in LDL samples.

Graphical abstract

In this paper we study the static structure and the dynamics of topological defects associated with isotropic droplets in nematic environment. Investigations were made in confined geometry of optical cells when the droplet size was of the order of or larger than the gap of the cell. We observed the coexistence of point boojums and Saturn ring or modified Saturn ring defects. We found transformation of the Saturn ring defect to two localized broad defects at increasing the droplet size. At droplet coalescence antipodes of point and localized broad defects were born and the dynamics of their annihilation with existing defects was investigated. We found strong difference in the process of annihilation of point and localized broad defects.

Graphical Abstract

Microscope images of isotropic droplets in nematic environment in a planar cell. The director orientation far from the droplets is in horizontal direction. The photographs were taken with crossed vertical and horizontal polarizers (a) and with a single horizontal polarizer (b). The cell thickness is 100 μm. Droplet diameter is less than the cell thickness. 1 and 2 are point boojums, L is the Saturn ring defect