Sequential detection of multiple phase transitions in model biological membranes using a red-emitting conjugated polyelectrolyte.

The anionic conjugated polyelectrolyte, poly[3-(6-sulfothioatehexyl)thiophene] (P3Anionic), functions as a highly sensitive probe of membrane order, uniquely capable of sequentially detecting the three key phase transitions occurring within model phospholipid bilayers. The observed sensitivity is the result of charge-mediated, selective localisation of P3Anionic within the head-groups of the phospholipid bilayer

Unlocking Structure-Self-Assembly Relationships in Cationic Azobenzene Photosurfactants.

Azobenzene photosurfactants are light-responsive amphiphiles that have garnered significant attention for diverse applications including delivery and sorting systems, phase transfer catalysis, and foam drainage. The azobenzene chromophore changes both its polarity and conformation (trans-cis isomerization) in response to UV light, while the amphiphilic structure drives self-assembly. Detailed understanding of the inherent relationship between the molecular structure, physicochemical behavior, and micellar arrangement of azobenzene photosurfactants is critical to their usefulness. Here, we investigate the key structure-function-assembly relationships in the popular cationic alkylazobenzene trimethylammonium bromide (AzoTAB) family of photosurfactants. We show that subtle changes in the surfactant structure (alkyl tail, spacer length) can lead to large variations in the critical micelle concentration, particularly in response to light, as determined by surface tensiometry and dynamic light scattering. Small-angle neutron scattering studies also reveal the formation of more diverse micellar aggregate structures (ellipsoids, cylinders, spheres) than predicted based on simple packing parameters. The results suggest that whereas the azobenzene core resides in the effective hydrophobic segment in the trans-isomer, it forms part of the effective hydrophilic segment in the cis-isomer because of the dramatic conformational and polarity changes induced by photoisomerization. The extent of this shift in the hydrophobic-hydrophilic balance is determined by the separation between the azobenzene core and the polar head group in the molecular structure. Our findings show that judicious design of the AzoTAB structure enables selective tailoring of the surfactant properties in response to light, such that they can be exploited and controlled in a reliable fashion

Multimodal Control of Liquid Crystalline Mesophases from Surfactants with Photoswitchable Tails

Non-invasive manipulation of the hierarchical structure of functional materials is a key challenge in the advancement of optoelectronics, energy conversion and storage devices and drug delivery systems. Here, using a combination of small-angle X-ray scattering and polarised optical microscopy, we decipher the various structure/self- assembly relationships of neutral surfactants bearing photoswitchable tails, which self-organise into a rich variety of lyotropic liquid crystalline mesophases. Facile, multimodal control of the nanoscale morphology of these single-component systems is achieved through: i) molecular structure, via careful selection of the alkyl tail/ethylene oxide headgroup lengths; ii) concentration; iii) temperature; and iv) photoisomerisation. The nanoscale architectures range from the weakly concentrated hyperswollen lamellar phases, the more common lyotropic lamellar and hexagonal phases, to pure thermotropic liquid crystals; all of which are accessible at room temperature. Photoisomerisation with UV light leads to the reversible destruction of the liquid crystalline phase, which can be spatially controlled through the use of a mask. This extensive study demonstrates the versatility of neutral photosurfactants and paves the way for them to be investigated for new applications, such as photoresponsive templates or drug delivery systems.Isaac Newton Trust/University of Cambridge Early Career Support Scheme grant. Irish Research Council EU COST action MP120

Charge-modulated self-assembly and growth of conjugated polyelectrolyte-polyoxometalate hybrid networks.

Self-assembly of an anionic polyoxometalate with cationic conjugated polyelectrolytes leads to hybrid supramolecular networks whose dimensionality is controlled by the chain length and steric charge distribution

Charge-Mediated Localization of Conjugated Polythiophenes in Zwitterionic Model Cell Membranes.

The selective engineering of conjugated polyelectrolyte (CPE)-phospholipid interfaces is poised to play a key role in the design of advanced biomedical and biotechnological devices. Herein, we report a strategic study to investigate the relationship between the charge of the CPE side group and their association with zwitterionic phospholipid bilayers. The interaction of dipalmitoylphosphatidylcholine (DPPC) phospholipid vesicles with a series of poly(thiophene)s bearing zwitterionic, cationic, or anionic terminal groups (P3Zwit, P3TMAHT and P3Anionic, respectively) has been probed. Although all CPEs showed an affinity for the zwitterionic vesicles, the calculated partition coefficients determined using photoluminescence spectroscopy suggested preferential incorporation within the lipid bilayer in the order P3Zwit > P3Anionic ≫ P3TMAHT. The polarity probe Prodan was used to further qualify the position of the CPE inside the vesicle bilayers via Förster resonance energy transfer (FRET) studies. The varying proximity of the CPEs to Prodan was reflected in the Stern-Volmer quenching constants and decreased in the order P3Anionic > P3TMAHT ≫ P3Zwit. Dynamic light scattering measurements showed an increase in the hydrodynamic diameter of the DPPC vesicles upon addition of each poly(thiophene), but to the greatest extent for P3Anionic. Small-angle neutron scattering studies also revealed that P3Anionic specifically increased the thickness of the headgroup region of the phospholipid bilayer. Epifluorescence and atomic force microscopy imaging showed that P3TMAHT formed amorphous agglomerates on the vesicle surface, P3Zwit was buried throughout the bilayer, and P3Anionic formed a shell of protruding chains around the surface, which promoted vesicle fusion. The global data indicate three distinctive modes of interaction for the poly(thiophene)s within DPPC vesicles, whereby the nature of the association is ultimately controlled by the pendant charge group on each CPE chain. Our results suggest that charge-mediated self-assembly may provide a simple and effective route to design luminescent CPE probes capable of specific localization within phospholipid membranes

Light-responsive self-assembly of a cationic azobenzene surfactant at high concentration.

The formation of high-concentration mesophases by a cationic azobenzene photosurfactant is described for the first time. Using a combination of polarised optical microscopy and small-angle X-ray scattering, optically anisotropic, self-assembled structures with long-range order are reported. The mesophases are disrupted or lost upon UV irradiation

Probing the dynamic self-assembly behaviour of photoswitchable wormlike micelles in real-time.

Understanding the dynamic self-assembly behaviour of azobenzene photosurfactants (AzoPS) is crucial to advance their use in controlled release applications such as drug delivery and micellar catalysis. Currently, their behaviour in the equilibrium cis- and trans-photostationary states is more widely understood than during the photoisomerisation process itself. Here, we investigate the time-dependent self-assembly of the different photoisomers of a model neutral AzoPS, tetraethylene glycol mono(4',4-octyloxy,octyl-azobenzene) (C8AzoOC8E4) using small-angle neutron scattering (SANS). We show that the incorporation of in situ UV-Vis absorption spectroscopy with SANS allows the scattering profile, and hence micelle shape, to be correlated with the extent of photoisomerisation in real-time. It was observed that C8AzoOC8E4 could switch between wormlike micelles (trans native state) and fractal aggregates (under UV light), with changes in the self-assembled structure arising concurrently with changes in the absorption spectrum. Wormlike micelles could be recovered within 60 seconds of blue light illumination. To the best of our knowledge, this is the first time the degree of AzoPS photoisomerisation has been tracked in situ through combined UV-Vis absorption spectroscopy-SANS measurements. This technique could be widely used to gain mechanistic and kinetic insights into light-dependent processes that are reliant on self-assembly

Making Good Tenure Decisions

This article provides information on decision making on the granting or denial of tenure to a faculty member. It not only has an effect on the professional life of a colleague, it has a major influence on the direction and long-term quality of the department. The tenure decision in made in the sixth year of a tenure-track faculty appointment. If a faculty member has been on the tenure track at two institutions, the years of service at the first institution usually count toward those six years, unless the faculty member and his of her current institution agree in writing at the time of appointment that they will not or that only a certain number of them will. The sooner the person is terminated or helped to find another position, the better for him or her and for the department

The Association of Patient Factors, Digital Access, and Online Behavior on Sustained Patient Portal Use: A Prospective Cohort of Enrolled Users

BACKGROUND: As electronic health records and computerized workflows expand, there are unprecedented opportunities to digitally connect with patients using secure portals. To realize the value of patient portals, initial reach across populations will need to be demonstrated, as well as sustained usage over time. OBJECTIVE: The study aim was to identify patient factors associated with short-term and long-term portal usage after patients registered to access all portal functions. METHODS: We prospectively followed a cohort of patients at a large Department of Veterans Affairs (VA) health care facility who recently completed identity proofing to use the VA patient portal. Information collected at baseline encompassed patient factors potentially associated with portal usage, including: demographics, Internet access and use, health literacy, patient activation, and self-reported health conditions. The primary outcome was the frequency of portal log-ins during 6-month and 18-month time intervals after study enrollment. RESULTS: A total of 270 study participants were followed prospectively. Almost all participants (260/268, 97.0%) reported going online, typically at home (248/268, 92.5%). At 6 months, 84.1% (227/270) of participants had visited the portal, with some variation in usage across demographic and health-related subgroups. There were no significant differences in portal log-ins by age, gender, education, marital status, race/ethnicity, distance to a VA facility, or patient activation measure. Significantly higher portal usage was seen among participants using high-speed broadband at home, greater self-reported ability using the Internet, and routinely going online. By 18 months, 91% participants had logged in to the portal, and no significant associations were found between usage and demographics, health status, or patient activation. When examining portal activity between 6 and 18 months, patients who were infrequent or high portal users remained in those categories, respectively. CONCLUSIONS: Short-term and long-term portal usage was associated with having broadband at home, high self-rated ability when using the Internet, and overall online behavior. Digital inclusion, or ready access to the Internet and digital skills, appears to be a social determinant in patient exposure to portal services

Structural characterization by scattering and spectroscopic methods and biological evaluation of polymeric micelles of poloxamines and TPGS as nanocarriers for miltefosine delivery

Miltefosine (MF), an alkylphospholipid originally developed for breast cancer treatment, is a highly active drug for the treatment against leishmaniasis, a neglected tropical disease considered the world’s second leading cause of death by a parasitic agent after malaria. MF exhibits dose-limiting gastrointestinal side effects in patients and its penetration through lipophilic barriers is reduced. In this work we propose a reformulation of MF by incorporating the drug to poly(ethylene)oxide (PEO)-based polymeric micelles, specifically, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Tetronic block copolymers (T904 and T1107). A full structural characterization of the aggregates has been carried out by SANS (small-angle neutron scattering) and dynamic light scattering (DLS), in combination with proton 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, to determine the precise location of the drug. The structure of MF micelles has been characterized as a function of the temperature and concentration. In the presence of the block-copolymers, MF forms mixed micelles in a wide range of temperatures, TPGS being the co-surfactant that incorporates more MF unimers. The hydrophobic tail of MF and those of the block copolymers are in close contact within the micelles, which present a core-shell structure with a hydrophilic corona formed by the PEG blocks of the TPGS and the zwitterion head group of the MF. In order to identify the best carrier, the antileishmanicidal activity of MF in the different formulations has been tested on macrophages, promastigotes and intracellular amastigotes. The combination of the three vehicles with MF makes the formulated drug more active than MF alone against L. major promastigotes, however, only the combination with T904 increases the MF activity against intracellular amastigotes. With the aim of exploring gel-based formulations of the drug, the combination of MF and T1107 under gelation conditions has also been investigated.The authors gratefully acknowledge the financial support provided by MINECO (Project MAT2014-59116-C2), Obra Social La Caixa (LCF/PR/PR13/11080005), University Carlos III Strategic Action in Composites materials and interphases 2011/00287/002, Fundación Caja Navarra, Gobierno de Navarra-Salud (12/2017), Fundación Roviralta, Ubesol, Government of Navarre, Laser Ebro, Inversiones Garcilaso de la Vega and COST actions CA18217 and CA18218. JCNS is acknowledged for the access to the KWS-2 diffractometer at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. J.P-R. also acknowledges the Asociación de Amigos de la Universidad de Navarra for his doctoral grant. This work benefited from the use of the SasView application, originally developed under NSF award DMR-0520547. Sasview contains code developed with funding from the European Union's Horizon 2020 research and innovation program under the SINE2020 project, grant agreement No 654000