DSPC - CAS 816-94-4

Amphiphilic lipid bilayers modify the friction properties of the surfaces on top of which they are deposited. In particular, the measured sliding friction coefficient can be significantly reduced compared with the native surface. We investigate in this work the friction properties of a numerical coarse-grained model of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) lipid bilayer subject to longitudinal shear. The interleaflet friction coefficient is obtained from out-of-equilibrium pulling or from relaxation simulations. In particular, we gain access to the transient viscoelastic response of a sheared bilayer. The bilayer mechanical response is found to depend significantly on the membrane physical state, with evidence in favor of a linear response regime in the fluid but not in the gel region. The linear response validity domain is established, and the timescales appearing in the membrane response discussed.

The membrane properties of phospholipid mixtures supported on silica were studied by means of a quartz crystal microbalance with dissipation monitoring (QCM-D) technique, in situ soft-contact atomic force microscopy (AFM), and friction force microscopy (FFM). The phospholipids used in this study were di-stearoylphosphatidylcholine (DSPC) and dilauroylphosphatidylcholine (DLPC). The phospholipid films were prepared by a vesicle-fusion method, in which DSPC/DLPC mixed liposomes dispersed in an aqueous medium are adsorbed on silica and their structure is transformed into a bilayer on the substrate. The changes in QCM-D (frequency and dissipation) and friction responses of DSPC single systems (gel state at 25°C) are relatively large compared with those of DLPC single systems (liquid-crystalline state at 25°C) and those of mixed DSPC/DLPC systems. This suggests that (i) the gel-state DSPC liposomes are somewhat flattened on the silica, by keeping their solid-like molecular rigidity, whereas (ii) both the liquid-crystalline DLPC and mixed liposomes experience instantaneous structural transformation at the silica/water interface and form a normally flattened bilayer on the substrate. The friction force response is dependent on the phase state of the phospholipids, and the liquid-crystalline DLPC has a more significant impact on the overall membrane properties (i.e., the degree of swelling and the friction response on the surface) than does the gel-state DSPC.

Nucleic acids, such as messenger RNAs, antisense oligonucleotides, and short interfering RNAs, hold great promise for treating previously 'undruggable' diseases. However, there are numerous biological barriers that hinder nucleic acid delivery to target cells and tissues. While lipid nanoparticles (LNPs) have been developed to protect nucleic acids from degradation and mediate their intracellular delivery, it is challenging to predict how alterations in LNP formulation parameters influence delivery to different organs. In this study, we utilized high-throughput in vivo screening to probe for structure-function relationships of intravenously administered LNPs along with quartz crystal microbalance with dissipation monitoring (QCM-D) to measure the binding affinity of LNPs to apolipoprotein E (ApoE), a protein implicated in the clearance and uptake of lipoproteins by the liver. High-throughput in vivo screening of a library consisting of 96 LNPs identified several formulations containing the helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) that preferentially accumulated in the liver, while identical LNPs that substituted DOPE with the helper lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) preferentially accumulated in the spleen. Using QCM-D, it was found that one DOPE-containing LNP formulation (LNP 42) had stronger interactions with ApoE than an identical LNP formulation that substituted DOPE with DSPC (LNP 90). In order to further validate our findings, we formulated LNP 42 and LNP 90 to encapsulate Cy3-siRNA or mRNA encoding for firefly luciferase. The DSPC-containing LNP (LNP 90) was found to increase delivery to the spleen for both siRNA (two-fold) and mRNA (five-fold). In terms of liver delivery, the DOPE-containing LNP (LNP 42) enhanced mRNA delivery to the liver by two-fold and improved liver transfection by three-fold. Understanding the role of the helper lipid in LNP biodistribution and ApoE adsorption may aid in the future design of LNPs for nucleic acid therapeutics.