@article{208,
  keywords = {Cationic PAMAM dendrimer, Channel formation, Excitable membrane, Functional toxicity, Nanoscale mechanism, Sodium permeability},
  author = {Gabriella Nyitrai and Tamás Keszthelyi and Attila Bóta and Ágnes Simon and Orsolya Tőke and Gergő Horváth and Ildikó Pál and Julianna Kardos and László Héja},
  title = {Sodium selective ion channel formation in living cell membranes by polyamidoamine dendrimer},
  abstract = {Abstract Polyamidoamine (PAMAM) dendrimers are highly charged hyperbranched protein-like polymers that are known to interact with cell membranes. In order to disclose the mechanisms of dendrimer–membrane interaction, we monitored the effect of PAMAM generation five (G5) dendrimer on the membrane permeability of living neuronal cells followed by exploring the underlying structural changes with infrared-visible sum frequency vibrational spectroscopy (SVFS), small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). G5 dendrimers were demonstrated to irreversibly increase the membrane permeability of neurons that could be blocked in low-[Na+], but not in low-[Ca2 +] media suggesting the formation of specific Na+ permeable channels. SFVS measurements on silica supported DPPG–DPPC bilayers suggested G5-specific trans-polarization of the membrane. SAXS data and freeze-fracture TEM imaging of self-organized DPPC vesicle systems demonstrated disruption of DPPC vesicle layers by G5 through polar interactions between G5 terminal amino groups and the anionic head groups of DPPC. We propose a nanoscale mechanism by which G5 incorporates into the membrane through multiple polar interactions that disrupt proximate membrane bilayer and shape a unique hydrophilic Na+ ion permeable channel around the dendrimer. In addition, we tested whether these artificial Na+ channels can be exploited as antibiotic tools. We showed that G5 quickly arrest the growth of resistant bacterial strains below 10 µg/ml concentration, while they show no detrimental effect on red blood cell viability, offering the chance for the development of new generation anti-resistant antibiotics.},
  year = {2013},
  journal = {Biochimica et Biophysica Acta (BBA) - Biomembranes},
  volume = {1828},
  number = {8},
  pages = {1873–1880},
  issn = {0005-2736},
  url = {http://www.sciencedirect.com/science/article/pii/S0005273613001168},
}