Biochemical Applications of the Positron Annihilation Techniques

Hill

et al. 2015

Positron annihilation lifetime spectroscopy (PALS) has been shown to be highly sensitive to conformational, structural and microenvironmental transformations arising from subtle geometric changes in molecular geometry in self-assembling biomimetic systems. The ortho-positronium (oPs) may be considered an active probe that can provide information on intrinsic packing and mobility within low molecular weight solids, viscous liquids, and soft matter systems. In this perspective we provide a critical overview of the literature in this field, including the evolution of analysis software and experimental protocols with commentary upon the practical utility of PALS. In particular, we discuss how PALS can provide unique insight into the macroscopic transport properties of several porous biomembrane-like nanostructures and suggest how this insight may provide information on the release of drugs from these matrices to aid in developing therapeutic interventions. We discuss the potentially exciting and fruitful application of this technique to membrane dynamics, diffusion and permeability. We propose that PALS can provide novel molecular level information that is complementary to conventional characterisation techniques.

Section: Application Of Pals To Biologically Relevant Systemsmentioning

confidence: 99%

Positron annihilation lifetime spectroscopy (PALS): a probe for molecular organisation in self-assembled biomimetic systems

Hill

et al. 2015

“…This bound state is referred to as a ''positronium'' that may exist in two ground states, i.e. [31][32][33][34][35][36][37] However studies of this nature have been sparse, with many of the observations conflicting due to differences in data analysis and experimental design, so that it is difficult to extract physicochemically-meaningful comparative information from these studies. 12 oPs is of the greatest interest as the primary mechanism of annihilation is via ''pick-off'' with electrons in low electron density regions.…”

Section: Introductionmentioning

confidence: 99%

Packing and mobility of hydrocarbon chains in phospholipid lyotropic liquid crystalline lamellar phases and liposomes: characterisation by positron annihilation lifetime spectroscopy (PALS)

Waddington

et al. 2015

Lipid lamellar mesophases and their colloidal dispersions (liposomes) are increasingly being deployed in vivo as drug delivery vehicles, and also as models of biological membranes in fundamental biophysics studies. The permeability and diffusion of small molecules such as drugs is accommodated by a change in local curvature and molecular packing (mesophase behaviour) of the bilayer membrane molecules. Positron annihilation lifetime spectroscopy (PALS) is capable of providing in situ molecular level information on changes in free volume and void space arising from such changes in a non-perturbative manner. In this work PALS was used to systematically characterise the temperature-induced melting transitions (Tm) of saturated and unsaturated phospholipid-water systems while systematically varying lipid chain length, as both bulk lamellar mesophase and as aqueous colloidal dispersions (liposomes). A four-component fit of the data was used that provides separate PALS lifetimes for the aqueous (τ3) and organic domains (τ4). The oPs lifetime (τ4), for the lamellar phases of DSPC (C18:0), DPPC (C16:0), DMPC (C14:0) and DLPC (C12:0) was found to be independent of chain length, with characteristic lifetime value τ4 ∼ 3.4 ns. τ4 is consistently larger in the dispersed liposomes compared to the bulk mesophases, suggesting that the hydrocarbon chains are more mobile. The use of contemporary and consistent analytical approaches as described in this study is the key to future deployment of PALS to interrogate the in situ influence of drugs on membrane and cellular microenvironments.

“…In recent years, positron annihilation lifetime spectroscopy (PALS) has demonstrated its utility as a molecular probe in soft condensed matter systems. 42,46 PALS techniques however, have not been broadly utilised by the amphiphile self-assembly community as the structural diversity displayed by amphiphiles, inherent heterogeneity and dynamic fluidity of these systems add complexity to the positron decay paths and data analysis. 37,[39][40][41][42][43][44][45] The decay of radioactive nuclei such as 22 Na leads to the generation of ortho-positroniums (oPs); where oPs lifetime (t oPs ) may be considered an active probe of both intrinsic packing and chain mobility.…”

Section: Introductionmentioning

confidence: 99%

Application of positron annihilation lifetime spectroscopy (PALS) to study the nanostructure in amphiphile self-assembly materials: phytantriol cubosomes and hexosomes

Waddington

et al. 2015

Self-assembled amphiphile nanostructures of colloidal dimensions such as cubosomes and hexosomes are of interest as delivery vectors in pharmaceutical and nanomedicine applications. Translation would be assisted through a better of understanding of the effects of drug loading on the internal nanostructure, and the relationship between this nanostructure and drug release profile. Positron annihilation lifetime spectroscopy (PALS) is sensitive to local microviscosity and is used as an in situ molecular probe to examine the Q2 (cubosome) → H2 (hexosome) → L2 phase transitions of the pharmaceutically relevant phytantriol-water system in the presence of a model hydrophobic drug, vitamin E acetate (VitEA). It is shown that the ortho-positronium lifetime (τ) is sensitive to molecular packing and mobility and this has been correlated with the rheological properties of individual lyotropic liquid crystalline mesophases. Characteristic PALS lifetimes for L2 (τ4∼ 4 ns) ∼ H2 (τ4∼ 4 ns) > Q(2 Pn3m) (τ4∼ 2.2 ns) are observed for the phytantriol-water system, with the addition of VitEA yielding a gradual increase in τ from τ∼ 2.2 ns for cubosomes to τ∼ 3.5 ns for hexosomes. The dynamic chain packing at higher temperatures and in the L2 and H2 phases is qualitatively less "viscous", consistent with rheological measurements. This information offers increased understanding of the relationship between internal nanostructure and species permeability.