Stochastic nanoroughness modulates neuron–astrocyte interactions and function via mechanosensing cation channels

• DOI: 10.1073/pnas.1412740111
• Publication Date: 2014-10-28T07:24:15Z
• Authors: Nils R. Blumenthal; Ola Hermanson; Bernd Heimrich; V. Prasad Shastri
• Keywords: Male; Neurons; 0303 health sciences; Spider Venoms; Cell Differentiation; Cell Communication; Mechanotransduction, Cellular; PC12 Cells; Rats; 03 medical and health sciences; Alzheimer Disease; Astrocytes; Animals; Humans; Intercellular Signaling Peptides and Proteins; Calcium Channels; Peptides

Extracellular soluble signals are known to play a critical role in maintaining neuronal function and homeostasis the CNS. However, CNS is also composed of extracellular matrix macromolecules glia support cells, contribution physical attributes these components maintenance regulation not well understood. Because possess well-defined topography, we theorize for topography development demonstrate that survival hippocampal neurons differentiation telencephalic neural stem cells modulated by nanoroughness. At roughnesses corresponding healthy astrocytes, dissociated survived independent from astrocytes showed superior functional traits (increased polarity calcium flux). Furthermore, differentiated into even under exogenous favor astrocytic differentiation. The decoupling seemed be triggered changes astrocyte apical-surface response Blocking signaling through mechanosensing cation channels using GsMTx4 negated ability sense nanoroughness promoted thus providing direct evidence nanotopography neuron-astrocyte interactions. We extrapolate neurodegenerative conditions show regions amyloid plaque buildup brain tissue Alzheimer's patients accompanied detrimental roughness. These findings suggest ECM-induced topographical pathologies provide new insights developing therapeutic targets engineering biomaterials.