Cylindrical Self-Assembly and Flow Alignment of Comb-Shaped Supramolecules of Electrically Conducting Polyaniline

Electrically conducting hexagonally self-assembled nanostructures of poly(aniline) (PANI) protonated with 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) and hydrogen bonded with resorcinol (res), 4-ethylresorcinol (C2res) or 4-hexylresorcinol (C6res) are studied. Small-angle X-ray scattering (SAXS) of PANI(AMPSA)0.5(Cnres)y with y = 0, ..., 1.5 indicate cylindrical self-assembly in all cases, and the long period depends on n and y. Addition of Cnres leads to plasticization and an increase of conductivity of up to ca. 4 orders of magnitude until saturation is achieved upon approaching y = 1. Simultaneously, the temperature gradient of the conductivity dσ/dT near the room temperature changes from positive to negative, which is reminescent to a transition from a thermally activated hopping-type to a more “metallic-like” behavior. It is suggested that, upon complexation with especially res and C2res, the PANI chains become progressively more confined in cylinders suggesting their stretching. Overall alignment of the local self-assembled domains was also aimed. In films, anisotropic overall structure and conductivity are observed upon pressing the “melt” samples between two glass plates. In more bulky samples, so far, large amplitude oscillating shear flow leads to biaxial structural anisotropy without observable conductivity anisotropy, potentially indicating the importance of residual defects for the transport properties.

The Reduced Folate Carrier (RFC) Is Cytotoxic to Cells under Conditions of Severe Folate Deprivation: RFC AS A DOUBLE EDGED SWORD IN FOLATE HOMEOSTASIS*

The reduced folate carrier (RFC), a bidirectional anion transporter, is the major uptake route of reduced folates essential for a spectrum of biochemical reactions and thus cellular proliferation. However, here we show that ectopic overexpression of the RFC, but not of folate receptor α, a high affinity unidirectional folate uptake route serving here as a negative control, resulted in an ∼15-fold decline in cellular viability in medium lacking folates but not in folate-containing medium. Moreover to explore possible mechanisms of adaptation to folate deficiency in various cell lines that express the endogenous RFC, we first determined the gene expression status of the following genes: (a) RFC, (b) ATP-driven folate exporters (i.e. MRP1, MRP5, and breast cancer resistance protein), and (c) folylpoly-γ-glutamate synthetase and γ-glutamate hydrolase (GGH), enzymes catalyzing folate polyglutamylation and hydrolysis, respectively. Upon 3–7 days of folate deprivation, semiquantitative reverse transcription-PCR analysis revealed a specific ∼2.5-fold decrease in RFC mRNA levels in both breast cancer and T-cell leukemia cell lines that was accompanied by a consistent fall in methotrexate influx, serving here as an RFC transport activity assay. Likewise a 2.4-fold decrease in GGH mRNA levels and ∼19% decreased GGH activity was documented for folate-deprived breast cancer cells. These results along with those of a novel mathematical biomodeling devised here suggest that upon severe short term (i.e. up to 7 days) folate deprivation RFC transport activity becomes detrimental as RFC, but not ATP-driven folate exporters, efficiently extrudes folate monoglutamates out of cells. Hence down-regulation of RFC and GGH may serve as a novel adaptive response to severe folate deficiency