Explaining SWNT-induced neurite outgrowth through the inhibition of endocytosis
One of the known effects of interfacing single walled carbon nanotubes (SWNTs) as scaffolds for neuron growth is that there is an extension of neurite length and a reduced number of dendrites. In Malarkey et al’s experiment, the SWNTs are made water soluble through the addition of a carboxylic acid group and then a reaction with glycol.
It is thought that these water soluble SWNTs affect neurite growth by reducing the flow of calcium ions into the cell during depolarization, which causes the cell to incorporate new membrane through vescicle fusion, exocytosis, and/or the inhibition of endocytosis.
In order to determine the exact mechanism at play, the researchers placed new rat hippocampal cells in culture, and treated this culture with either SWNTs or a control treatment. In order to test for the amount of endocytosis, the researchers treated these cultures with FM1-43 dye, which does not passively diffuse across the cell membrane and must be taken up via endocytosis. They initially found no difference in the amount of dye uptake between cells exposed to SWNTs and those not exposed.
However, upon subsequent tests, it was determined that SWNTs did affect the amount of die present in the cells, but only in the vescicles (”regulated/stimulated”), not the intracellular area itself (”constitutional”). Therefore, the authors hypothesize that the SWNTs affect neurite growth by inhibiting the endocytotic facet of vescicular recycling.
It doesn’t make sense that the increased membrane area would occur through increased exotycosis since exotycosis is a calcium dependent process and the application of SWNTs have been shown to decrease the amount of calcium in the cell.
Every aspect of carbon nanotube impact on neurons will have to be carefully examined before they can be ethically applied to a living human brain. If increased neurite growth is found to be a detrimental effect, perhaps it could be managed by stimulating endocytosis via vescicles in another way to counteract the effect of SWNTs.
Reference
Malarkey EB, Reyes RC, Zhao B, Haddon RC, Parpura V. 2008 Water soluble single-walled carbon nanotubes inhibit stimulated endocytosis in neurons. Nano Letters 8: 3538–3542. doi:10.1021/nl8017912.