The sorptive properties of clay are harnessed to provide niches for tissue regeneration. Synthetic smectite clays self‐organize into gels under physiological conditions to allow encapsulation of ...cells and demonstrate remarkable capacity for the localization of biological molecules without the need for complex chemical modifications.
Phytoplankton replace phosphorus-containing lipids (P-lipids) with non-P analogues, boosting growth in P-limited oceans. In the model diatom
, the substitution dynamics of lipid headgroups are well ...described, but those of the individual lipids, differing in fatty acid composition, are unknown. Moreover, the behavior of lipids outside the common headgroup classes and the relationship between lipid substitution and cellular particulate organic P (POP) have yet to be reported. We investigated these through the mass spectrometric lipidomics of P-replete (P
) and P-depleted (P
)
cultures. Nonlipidic POP was depleted rapidly by the initiation of P stress, followed by the cessation of P-lipid biosynthesis and per-cell reductions in the P-lipid levels of successive generations. Minor P-lipid degradative breakdown was observed, releasing P for other processes, but most P-lipids remained intact. This may confer an advantage on efficient heterotrophic lipid consumers in P-limited oceans. Glycerophosphatidylcholine (PC), the predominant P-lipid, was similar in composition to its betaine substitute lipid. During substitution, PC was less abundant per cell and was more highly unsaturated in composition. This may reflect underlying biosynthetic processes or the regulation of membrane biophysical properties subject to lipid substitution. Finally, levels of several diglycosylceramide lipids increased as much as 10-fold under P stress. These represent novel substitute lipids and potential biomarkers for the study of P limitation
, contributing to growing evidence highlighting the importance of sphingolipids in phycology. These findings contribute much to our understanding of P-lipid substitution, a powerful and widespread adaptation to P limitation in the oligotrophic ocean.
Unicellular organisms replace phosphorus (P)-containing membrane lipids with non-P substitutes when P is scarce, allowing greater growth of populations. Previous research with the model diatom species
grouped lipids by polar headgroups in their chemical structures. The significance of the research reported here is threefold. (i) We described the individual lipids within the headgroups during P-lipid substitution, revealing the relationships between lipid headgroups and hinting at the underlying biochemical processes. (ii) We measured total cellular P, placing P-lipid substitution in the context of the broader response to P stress and yielding insight into the implications of substitution in the marine environment. (iii) We identified lipids previously unknown in this system, revealing a new type of non-P substitute lipid, which is potentially useful as a biomarker for the investigation of P limitation in the ocean.
The lyotropic liquid crystalline phases of surfactants exhibit a rich polymorphism of structures that have long-range periodicities and whose characteristic repeat distances range from 2 to 15 ...nanometers. The electrochemical reduction of platinum salts confined to the aqueous environments of these phases leads to the deposition of platinum films that have a well-defined long-ranged porous nanostructure and high specific surface areas. These results suggest that the use of liquid crystalline plating solutions could be a versatile way to create mesoporous electrodes for batteries, fuel cells, electrochemical capacitors, and sensors.
Mixtures of dsDNA and lipids, so-called lipoplexes, are widely used as less toxic alternatives to viral vectors in transfection studies. However, the transfection efficiency achieved by lipoplexes is ...significantly lower than that of viral vectors and is a barrier to their use in the clinic. There is now significant evidence suggesting that the molecular organization and structure (nanoarchitecture) of lipoplexes might correlate with biological activity. As a consequence, the ability to predict quantitatively the nanoarchitecture of new systems, and how these might change intracellularly, would be a major tool in the development of rational discovery strategies for more efficient lipoplex formulations. Here we report the use of a coarse-grain molecular dynamics simulation to predict the phases formed by two lipoplex systems: dsDNA-DOPE and dsDNA-DOPE-DOTAP. The predictions of the simulations show excellent agreement with experimental data from polarized light microscopy and small-angle X-ray diffraction (SAXS); the simulations predicted the formation of phases with d-spacings that were comparable to those measured by SAXS. More significantly, the simulations were able to reproduce for the first time the experimentally observed change from a fluid lamellar to an inverse hexagonal phase in the dsDNA-DOPE-DOTAP system as a function of changes in lipid composition. Our studies indicate that coarse-grain MD simulations could provide a powerful tool to understand, and hence design, new lipoplex systems.
Neuropeptide Y (NPY) is widely expressed in the central and peripheral nervous systems and is proliferative for a range of cells types in vitro. NPY plays a key role in regulating adult hippocampal ...neurogenesis in vivo under both basal and pathological conditions, although the underlying mechanisms are largely unknown. We have investigated the role of nitric oxide (NO) on the neurogenic effects of NPY. Using postnatal rat hippocampal cultures, we show that the proliferative effect of NPY on nestin+ precursor cells is NO-dependent. As well as the involvement of neuronal nitric-oxide synthase, the proliferative effect is mediated via an NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) and extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. We show that NPY-mediated intracellular NO signaling results in an increase in neuroproliferation. By contrast, extracellular NO had an opposite, inhibitory effect on proliferation. The importance of the NO-cGMP-PKG signaling pathway in ERK1/2 activation was confirmed using Western blotting. This work unites two significant modulators of hippocampal neurogenesis within a common signaling framework and provides a mechanism for the independent extra- and intracellular regulation of postnatal neural precursors by NO.
Neuropeptide Y and nitric oxide are key regulators of adult hippocampal neurogenesis.
Pharmacological inhibition of intracellular NO signaling pathways abolished neuropeptide Y-mediated neuroproliferation.
An intracellular NO-cGMP-PKG and ERK pathway mediates the neuropeptide Y neuroproliferative effect.
This work unites two significant modulators of hippocampal neurogenesis and provides a mechanism for the independent extra- and intracellular regulation of postnatal neural precursors by NO.
The addition of saturated fatty acids (FA) to phosphatidylcholine lipids (PC) that have saturated acyl chains has been shown to promote the formation of lyotropic liquid-crystalline phases with ...negative mean curvature. PC/FA mixtures may exhibit inverse bicontinuous cubic phases (Im3m, Pn3m) or inverse topology hexagonal phases (HII), depending on the length of the acyl chains/fatty acid. Here we report a detailed study of the phase behavior of binary mixtures of dioleoylphosphatidylcholine (DOPC)/oleic acid (OA) and dioleoylphosphatidylethanolamine (DOPE)/oleic acid at limiting hydration, constructed using small-angle X-ray diffraction (SAXD) data. The phase diagrams of both systems show a succession of phases with increasing negative mean curvature with increasing OA content. At high OA concentrations, we have observed the occurrence of an inverse micellar Fd3m phase in both systems. Hitherto, this phase had not been reported for phosphatidylethanolamine/fatty acid mixtures, and as such it highlights an additional route through which fatty acids may increase the propensity of bilayer lipid membranes to curve. We also propose a method that uses the temperature dependence of the lattice parameters of the HII phases to estimate the spontaneous radii of curvature (R0) of the binary mixtures and of the component lipids. Using this method, we calculated the R0 values of the complexes comprising one phospholipid molecule and two fatty acid molecules, which have been postulated to drive the formation of inverse phases in PL/FA mixtures. These are -1.8 nm (±0.4 nm) for DOPC(OA)2 and -1.1 nm (±0.1 nm) for DOPE(OA)2. R0 values estimated in this way allow the quantification of the contribution that different lipid species make to membrane curvature elastic properties and hence of their effect on the function of membrane-bound proteins.
The activity of CTP:phosphocholine cytidylyltransferase, a rate-limiting enzyme in phosphatidylcholine biosynthesis, is modulated by its interaction with lipid bilayers Kent, C. (1997) Biochim. ...Biophys. Acta 1348, 79-90. Its regulation is of central importance in the maintenance of membrane lipid homeostasis. Here we show evidence that the stored curvature elastic stress in the lipid membrane's monolayer modulates the activity of CTP:phosphocholine cytidylyltransferase. Our results show how a purely physical feedback signal could play a key role in the control of membrane lipid synthesis.
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