Dense ion clouds attracted by supercharged supramolecular polymers boost development of neurons

Neuronal circuitry is critically dependent on the controlled transport of ions in and out of cells. We report here a strategy to supercharge a nanoscale supramolecular assembly that can harbor a huge concentration of monovalent ions which enhances neuronal development. This was accomplished by embedding a small organic cation in a negatively charged peptide amphiphile nanostructure that leads to full ionization of all monomers without destroying the supramolecular polymer. We cultured mouse and human neurons on the supercharged filaments covered by dense ion clouds and observed rapid neurite branching and functional maturation. Furthermore, rat hippocampal brain slices revealed that the dense ion clouds can increase and sustain the frequency of action potential propagation. Our study has provided a vision for the potential use of synthetic systems to boost neurotransmission. Overall design: To investigate the molecular cascades trigerred by our ion-charged nanostructures (ICNs), we treated embryonic mouse cortical neurons with Na+ ICNs or K+ ICNs and compared their relative gene expression changes to non-charged peptide amphiphiles 72 hrs after treatment.Gene expression profiling was performed using single-end RNA-Seq data obtained from 3 biological replicates per condition.