|Title||Sodium selective ion channel formation in living cell membranes by polyamidoamine dendrimer|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Nyitrai, G, Keszthelyi, T, Bóta, A, Simon, Á, Tőke, O, Horváth, G, Pál, I, Kardos, J, Héja, L|
|Journal||Biochimica et Biophysica Acta (BBA) - Biomembranes|
|Keywords||Cationic PAMAM dendrimer, Channel formation, Excitable membrane, Functional toxicity, Nanoscale mechanism, Sodium permeability|
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 dendrimerâ€“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 DPPGâ€“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 Î¼g/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.