3 research outputs found
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A design and synthesis of model membrane systems for probing lipid-polyphenol interactions
Modelling cellular membranes is crucial to understand how their structure
affects function. Further, to investigate membrane-target interactions, accurate
biological membrane models are essential. Understanding membrane interactions
in this way has applications for in vivo processes, pharmaceutics and medicine,
nutrition, and agriculture among others. This thesis presents research findings
for two particular kinds of model membranes, bacterial and epithelial, and their
interactions with a series of polyphenolic compounds. A distinction is made
within about the nature of the “models”, where some models referred to are
physical in nature, and others are computational or mathematical models. The
epithelial model becomes focused on the human gastrointestinal epithelium.
Here the lipid composition of this novel model epithelial membrane presented is
the most complex and accurate model published to date.
This work emphasises the importance of developing more complex model
membranes for biological studies. This research aims to bridge the gap between
their study and the ability to use surface sensitive techniques to measure
membranes and their interactions. Similarly, the benefits of polyphenolic
compounds are identified, and some polyphenols whose mechanism of action
is relatively poorly understood are investigated in order to move towards
developing structure-activity relationships.
Analysis of model membranes through development and interaction with
polyphenolic compounds is achieved through complementary surface sensitive
techniques that allow lipid bilayer formation and interaction with polyphenols to
be measured. Development of the lipid composition of the model bacterial and
epithelial membranes takes place through analysis of single lipid components
and investigates the effects of mixing lipids within model membranes through
calorimetric and surface pressure measurements. Determination of polyphenol
presence at a membrane interface, real-time measurement of mass changes for
membrane formation and polyphenol interaction, and most crucially structural
resolution of interactions in the nanometer regime are achieved using state of
the art supported and floating lipid membranes.
Mechanisms by which interaction of polyphenols with model biological
lipid membranes is explored, with a comparison between bacterial and
epithelial membranes highlighted to show variation in polyphenol interaction
with membranes of differing phospholipid composition. The effects of lipid
composition of membranes is studied using epithelial membranes of iteratively
more complex and accurate composition, with membrane composition
informed by a thorough meta-analysis of epithelial membrane lipid headgroup
composition. We are able to show two different modes of action of polyphenols
within membranes depending on the type and lipid composition of the
membrane where nuances of polyphenol interaction are rationalised in terms of
the molecular properties of the polyphenol under investigation.
Bacterial model membranes, both physically and computationally, show
strong and persistent interactions under flow with (-)-epigallocatechin gallate
and Tellimagrandin-II, when characterised by neutron reflectometry. In the case
of Tellimagrandin-II, apparent membrane lysis is observed with multilamellar
membrane stacking occurring in the sample cell. By contrast, the epithelial
membrane shows binding to the surface of, and intercalation into the tail region,
of the membrane. The differences between these two modes of interaction have
important implications where the dietary, pharmaceutical, and antimicrobial
properties of these compounds is concerned
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Interactions of galloylated polyphenols with a simple gram-negative bacterial membrane lipid model
Differential scanning calorimetry (DSC) was used to explore the interactions of isolated polyphenolic compounds, including (-)-epigallocatechin gallate ((-)-EGCg), tellimagrandins I and II (Tel-I and Tel-II), and 1,2,3,4,6-penta-O-galloyl-D-glucose (PGG), with a model Gram-negative bacterial membrane with a view to investigating their antimicrobial properties. The model membranes comprised 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (DPPG), fabricated to mimic the domain formation observed in natural membranes, as well as ideally mixed lipid vesicles for the interaction with (-)-EGCg. Polyphenols induced changes in lipid mixing/de-mixing depending on the method of vesicle preparation, as was clearly evidenced by alterations in the lipid transition temperatures. There was a distinct affinity of the polyphenols for the DPPG lipid component, which was attributed to the electrostatic interactions between the polyphenolic galloyl moieties and the lipid headgroups. These interactions were found to operate through either the stabilization of the lipid headgroups by the polyphenols or the insertion of the polyphenols into the membrane itself. Structural attributes of the polyphenols,
including the number of galloyl groups, the hydrophobicity quantified by partition coefficients (logP), and structural flexibility, exhibited a correlation with the temperature transitions observed in the DSC measurements. This study furthers our understanding of the intricate interplay between the structural features of polyphenolic compounds and their interactions with model bacterial membrane
vesicles towards the exploitation of polyphenols as antimicrobials
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Infrared spectra and optical constants of astronomical ices: III. Propane, propylene, and propyne
Infrared (IR) spectra of the hydrocarbon ices C3H8 (propane), C3H6 (propylene, propene), and C3H4 (propyne, methylacetylene) are relevant to the study of the low-temperature chemistry and spectroscopy of objects within and beyond the Solar System, but IR band strengths and absorption coefficients are lacking for these compounds. Here we present new IR spectra of crystalline and non-crystalline forms of C3H8, C3H6, and C3H4. Measurements of ice density and refractive index also are reported, two quantities needed to compute IR absorption coefficients, band strengths, optical constants, and, ultimately, abundances of propane, propylene, and propyne in extraterrestrial environments and in laboratory experiments. Suggestions and interpretations are offered regarding the multiple crystalline forms of propane and propylene observed. Applications and extensions are described