Understanding how the Antibiotic Amphotericin works
Amphotericin has been the first line of defence against fungal infections since the mid-1950s. Unfortunately, resistance to this drug is beginning to emerge, posing serious problems for AIDS and chemotherapy patients who often suffer potentially fatal fungal infections. Normally, replacement drugs would be sought by examining compounds with a similar mechanism of action. For amphotericin, though, this is difficult. It is established that the drug punches holes in cells, which makes them leaky and so causes them to die, but how it does this and why it causes more damage to fungal cells than human cells remains unclear.
Neutron reflectivity and small-angle scattering studies at ISIS have been performed to study the effects of amphotericin on model human and fungal cell membranes, to find out why the drug is so selective.
Rather surprisingly, the drug is found to insert into both fungal and human cell membranes but the neutron studies also clearly show that it perturbs these two types of membranes in markedly different ways.
F Foglia (King's College), A F Drake (King's College), A E Terry (ISIS), S E Rogers (ISIS), M J Lawrence (King's College), D J Barlow (King's College)
Biochimica et Biophysica Acta (2011), Volume 1808, Pages 1574-1580
Quantifying Order in Liquid Crystals
A key quantity in liquid crystal science is the orientational order parameter. It is the parameter that distinguishes the nematic phase from an isotropic liquid and it is ubiquitous in the liquid crystal literature. This paper provides a relatively simple method to determine the translational order parameter of a smectic liquid crystal from measurements of the absolute intensity of the first-order layer reflection from an unaligned (powder) sample using small-angle neutron scattering (SANS).
(The paper was one of just 8 published by the journal Liquid Crystals to be 'highly commended' by the selection committee for the 2010 Luckhurst-Samulski Prize. In the words of the journal editor 'The eight papers shortlisted for the Prize were truly of the highest quality and the committee found choosing between them a very difficult task'. All the shortlisted papers have been made free to access by the Publishers.)
G G Alexander (Bristol), S M King (ISIS), R M Richardson (Bristol) & H Zimmermann (MPI Heidelberg)
Liquid Crystals (2010), Volume 37, Issue 6/7, Pages 961-968
Natural Aquatic Nanocolloids
Aquatic colloids (naturally occurring heterogeneous mixtures of mineral particles and organic components at submicrometer length scales) are of major environmental importance as vectors for transport of nutrients, trace metals, and organic micropollutants, and in the biogeochemical cycling and bioavailability of these pollutants. Developments in colloid fractionation (e.g., field flow) and imaging techniques (e.g., ESEM, ETEM, and AFM) have greatly improved our view of colloidal structure in natural systems, however there remain major problems understanding how that structure relates to colloid composition, stability, and interactions in aqueous suspensions and how it influences chemical and biological reactivity.
Here the potential of small-angle neutron scattering (SANS) as a new quantitative tool for studying nanostructure and length scales in a range of natural colloidal dispersions has been examined. The results show that natural aquatic colloids are generally fractal with 3D network-type structures. None of these structures are consistent with diffusion-limited (DLCA) or reaction-limited (RLCA) particle-particle aggregation processes. The results also suggest three characteristic length scales: one ca. 3-10 nm, which is identified with “primary particle” sizes, another of ca. 20-50 nm suggestive of small aggregates, and the last ca. 50-200 nm which is postulated to arise from transient networks of the aggregates.
H P Jarvie (Centre for Ecology & Hydrology) & S M King (ISIS)
Environmental Science & Technology (2007), Volume 41, Pages 2868-2873
Real-time SANS study of transient phases in polymer crystallization
Polymers such as polyethylene, polypropylene and nylon form thin (10-50 nm) crystalline lamellae separated by an amorphous layer. Because polymer molecules are very long, their crystallization is a highly non-equilibrium process and it is often accompanied by the appearance of transient forms and solid-state transformations. The understanding of these meta-stable structures is critical to the control of polymer processing. Recent work explores the possibility of real-time SANS at ISIS, applying it to the study of transient phases in polymer crystallization with a view to extending the technique to other dynamic systems.
Some of the transient phases in polymer crystallization can be very short lived, for example, the transient non-integer folded form, or NIF, observed in pure long chain linear alkanes by real-time SAXS. Although SANS normally requires long exposure times (usually hours), our recent experiments on long alkane C12D25C192H384CHDC11D23 have shown that SANS spectra with reasonable signal-noise ratio can be collected in seconds. This makes the material an ideal testing system for the real-time technique. In addition, a proper grasp of the transient NIF form and its subsequent transformation would help understand the technologically-important processes of primary and secondary crystallization of polymers.
X B Zeng, G Ungar (University of Sheffield)), S J Spells (Sheffield Hallam University) and S M King (ISIS)
Macromolecules (2005), Volume 38, Issue 17, Pages 7201-7204
Hanging by a Thread
Ropes are much more widely used than many people realise, finding applications in the construction, conservation, inspection, marine and leisure arenas. Modern high performance ropes are today made from synthetic polymers rather than sisel or hemp. But even so they are still susceptible to chemical and physical degradation. The consequences of a rope failure would be very serious, but assessing the condition of a rope is actually quite difficult. The only way to really test if a rope will perform as intended is to conduct a dynamic load test. But this is of course destructive testing and only provides limited information. Soiled ropes present another worry, that of how best to clean them. Even though the fibres are essentially those used in textiles and carpets, manufacturers are very circumspect about endorsing the use of detergents.
Neutron scattering is providing insights into the microstructural changes of the polymer fibres with different types of chemical and physical ageing. Its aim is to provide a molecular-level understanding of ageing phenomena that can then be used to improve rope care.
Small-Angle Neutron Scattering (SANS) has been used to investigate samples of commercially produced climbing and abseil ropes made from polyamides, typically nylon-6 and nylon-6/6, soaked in solutions of D2O containing different deuterated solutes; anionic, cationic and non-ionic surfactants (representative constituents of laundry detergents and fabric conditioners), and sulphuric acid (known to degrade nylon). Nylons are in fact semi-crystalline polymers where regions of amorphous (“low density”) polymer link together highly crystalline (“high density”) lamellae to form a lamellar stack. Changes in the density of these regions can be probed by SANS.
S M King (ISIS) & D G Bucknall (University of Oxford)
Polymer (2005), Volume 46, Issue 25, Pages 11424-11434
Microstructure of complex fluids
Many everyday household and personal care products are complex formulations which exhibit a rich behaviour. The processing and formulation of such products – which include fabric conditioners, shampoos and shower gels – are more controllable if their microstructure is understood. Small angle neutron scattering at ISIS has proved to be a valuable tool for investigation of such fluids, and results are now being applied to optimisation of processing protocols. Specifically, many of these formulations are in the form of lamella phase dispersions and undergo structural phase transitions and changes in orientational order with shear flow. These lamella phase dispersions exhibit a liquid-like to semi-solid transition as a function of temperature, and this transition has a significant impact upon the in-use microstructure. SANS measurements during shear flow above and below the transition temperature of a di-chain cationic surfactant have enabled energy and time savings during in- production product processing.