1,053 research outputs found
Polyelectrolyte Multilayering on a Charged Planar Surface
The adsorption of highly \textit{oppositely} charged flexible
polyelectrolytes (PEs) on a charged planar substrate is investigated by means
of Monte Carlo (MC) simulations. We study in detail the equilibrium structure
of the first few PE layers. The influence of the chain length and of a (extra)
non-electrostatic short range attraction between the polycations and the
negatively charged substrate is considered. We show that the stability as well
as the microstructure of the PE layers are especially sensitive to the strength
of this latter interaction. Qualitative agreement is reached with some recent
experiments.Comment: 28 pages; 11 (main) Figs - Revtex4 - Higher resolution Figs can be
obtained upon request. To appear in Macromolecule
POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart
The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain-containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP-dependent binding and regulation of TREK-1 potassium channels. We show that TREK-1 binds the AC9:POPDC1 complex and copurifies in a POPDC1-dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP-independent, TREK-1 association with AC9 and POPDC1 is reduced upon stimulation of the β-adrenergic receptor (βAR). AC9 activity is required for βAR reduction of TREK-1 complex formation with AC9:POPDC1 and in reversing POPDC1 enhancement of TREK-1 currents. Finally, deletion of the gene-encoding AC9 (Adcy9) gives rise to bradycardia at rest and stress-induced heart rate variability, a milder phenotype than the loss of Popdc1 but similar to the loss of Kcnk2 (TREK-1). Thus, POPDC1 represents a novel adaptor for AC9 interactions with TREK-1 to regulate heart rate control
Multiple Scale Reorganization of Electrostatic Complexes of PolyStyrene Sulfonate and Lysozyme
We report on a SANS investigation into the potential for these structural
reorganization of complexes composed of lysozyme and small PSS chains of
opposite charge if the physicochemical conditions of the solutions are changed
after their formation. Mixtures of solutions of lysozyme and PSS with high
matter content and with an introduced charge ratio [-]/[+]intro close to the
electrostatic stoichiometry, lead to suspensions that are macroscopically
stable. They are composed at local scale of dense globular primary complexes of
radius ~ 100 {\AA}; at a higher scale they are organized fractally with a
dimension 2.1. We first show that the dilution of the solution of complexes,
all other physicochemical parameters remaining constant, induces a macroscopic
destabilization of the solutions but does not modify the structure of the
complexes at submicronic scales. This suggests that the colloidal stability of
the complexes can be explained by the interlocking of the fractal aggregates in
a network at high concentration: dilution does not break the local aggregate
structure but it does destroy the network. We show, secondly, that the addition
of salt does not change the almost frozen inner structure of the cores of the
primary complexes, although it does encourage growth of the complexes; these
coalesce into larger complexes as salt has partially screened the electrostatic
repulsions between two primary complexes. These larger primary complexes remain
aggregated with a fractal dimension of 2.1. Thirdly, we show that the addition
of PSS chains up to [-]/[+]intro ~ 20, after the formation of the primary
complex with a [-]/[+]intro close to 1, only slightly changes the inner
structure of the primary complexes. Moreover, in contrast to the synthesis
achieved in the one-step mixing procedure where the proteins are unfolded for a
range of [-]/[+]intro, the native conformation of the proteins is preserved
inside the frozen core
The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains
We have investigated the contribution to ionic
selectivity of residues in the selectivity filter and pore
helices of the P1 and P2 domains in the acid sensitive
potassium channel TASK-1. We used site directed mutagenesis
and electrophysiological studies, assisted by structural
models built through computational methods. We have
measured selectivity in channels expressed in Xenopus
oocytes, using voltage clamp to measure shifts in reversal
potential and current amplitudes when Rb+ or Na+ replaced
extracellular K+. Both P1 and P2 contribute to selectivity,
and most mutations, including mutation of residues in the
triplets GYG and GFG in P1 and P2, made channels nonselective.
We interpret the effects of these—and of other
mutations—in terms of the way the pore is likely to be
stabilised structurally. We show also that residues in the
outer pore mouth contribute to selectivity in TASK-1.
Mutations resulting in loss of selectivity (e.g. I94S, G95A)
were associated with slowing of the response of channels to
depolarisation. More important physiologically, pH sensitivity
is also lost or altered by such mutations. Mutations
that retained selectivity (e.g. I94L, I94V) also retained their
response to acidification. It is likely that responses both to
voltage and pH changes involve gating at the selectivity filter
The future of layer-by-layer assembly: A tribute to ACS Nano associate editor Helmuth Möhwald
Layer-by-layer (LbL) assembly is a widely used tool for engineering materials and coatings. In this Perspective, dedicated to the memory of ACS Nano associate editor Prof. Dr. Helmuth Möhwald, we discuss the developments and applications that are to come in LbL assembly, focusing on coatings, bulk materials, membranes, nanocomposites, and delivery vehicles
Impact of Collagen/Heparin Multilayers for Regulating Bone Cellular Functions
Bone cell interaction with extracellular matrix (ECM) microenvironment is of critical importance when engineering surface interfaces for bone regeneration. In this work layer-by-layer films of type I collagen (coll), the major constituent of bone ECM, and heparin (hep), a glycosaminoglycan, were assembled on poly(l-lactic acid) (PLLA) substrates to evaluate the impact of the biomacromolecular coating on cell activity. The surface modification of PLLA demonstrated that the hep/coll multilayer is stable after 10 bilayers (confirmed by contact angle, infrared spectroscopy, and morphological analysis). This simple approach provided novel information on the effect of heparin on type I collagen hierarchical organization and subsequent cell response of osteoblast-like (MC3T3-E1) and human bone marrow-derived mesenchymal stem cells (hMSCs). Interestingly, the number of deposited heparin layers (1 or 10) appeared to play an important role in the self-assembly of collagen into fibrils, stabilizing the fibrous collagen layer, and potentially impacting hMSCs activity.Ana M. Ferreira thanks the Lagrange CRT for financing her researc
Ultra-soft 100 nm Thick Zero Poisson’s Ratio Film with 60% Reversible Compressibility
About a 100 nm thick multilayer film of nanoparticle monolayers and polymer layers is shown to behave like cellular-foam with a modulus below 100 KPa. The 1.25 cm radius film adhered to a rigid surface can be compressed reversibly to 60% strain. The more than four orders of magnitude lower modulus compared to its constituents is explained by considering local bending in the (nano)cellular structure, similar to cork and wings of beetles. As the rigidity of the polymer backbone is increased in just four monolayers the modulus of the composite increases by over 70%. Electro-optical map of the strain distribution over the area of compression and increase in modulus with thickness indicates the films have zero Poisson’s ratio
Compact Polyelectrolyte Complexes: “Saloplastic” Candidates for Biomaterials
Precipitates of polyelectrolyte complexes were transformed into rugged shapes suitable for bioimplants by ultracentrifugation in the presence of high salt concentration. Salt ions dope the complex, creating a softer material with viscous fluid-like properties. Complexes that were compacted under the centrifugal field (CoPECs) were made from poly(diallyldimethyl ammonium), PDADMA, as polycation, and poly(styrene sulfonate), PSS, or poly(methacrylic acid), PMAA, as polyanion. Dynamic mechanical testing revealed a rubbery plateau at lower frequencies for PSS/PDADMA with moduli that decreased with increasing salt concentration, as internal ion pair cross-links were broken. CoPECs had significantly lower modulii compared to similar polyelectrolyte complexes prepared by the “multilayering ” method. The difference in mechanical properties was ascribed to higher water content (located in micropores) for the former and, more importantly, to their nonstoichiometric polymer composition. The modulus of PMAA/PDADMA CoPECs, under physiological conditions, demonstrated dynamic mechanical properties that were close to those of the nucleus pulposus in an intervertebral disk
Hypertonicity-induced cation channels rescue cells from staurosporine-elicited apoptosis
Cell shrinkage is one of the earliest events during apoptosis. Cell shrinkage also occurs upon hypertonic stress, and previous work has shown that hypertonicity-induced cation channels (HICCs) underlie a highly efficient mechanism of recovery from cell shrinkage, called the regulatory volume increase (RVI), in many cell types. Here, the effects of HICC activation on staurosporine-induced apoptotic volume decrease (AVD) and apoptosis were studied in HeLa cells by means of electronic cell sizing and whole-cell patch-clamp recording. It was found that hypertonic stress reduces staurosporine-induced AVD and cell death (associated with caspase-3/7 activation and DNA fragmentation), and that this effect was actually due to activation of the HICC. On the other hand, staurosporine was found to significantly reduce osmotic HICC activation. It is concluded that AVD and RVI reflect two fundamentally distinct functional modes in terms of the activity and role of the HICC, in a shrunken cell. Our results also demonstrate, for the first time, the ability of the HICC to rescue cells from the process of programmed cell death
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