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Nano Lett. 2019 Mar 13;19(3):1451-1459. doi: 10.1021/acs.nanolett.8b03879. Epub 2019 Feb 7.

Comparing Transcriptome Profiles of Neurons Interfacing Adjacent Cells and Nanopatterned Substrates Reveals Fundamental Neuronal Interactions.

Baranes K1,2, Hibsh D2,3, Cohen S1,2,4, Yamin T2,5, Efroni S2,3, Sharoni A2,5, Shefi O1,2.

Author information

1
Faculty of Engineering , Bar-Ilan University , Ramat-Gan 5290002 , Israel.
2
Bar-Ilan Institute of Nanotechnology and Advanced Materials , Bar-Ilan University , Ramat-Gan 5290002 , Israel.
3
Faculty of Life Sciences , Bar-Ilan University , Ramat-Gan 5290002 , Israel.
4
Gonda Multidisciplinary Brain Research Center , Bar-Ilan University , Ramat-Gan 5290002 , Israel.
5
Department of Physics , Bar-Ilan University , Ramat-Gan 5290002 , Israel.

Abstract

Developing neuronal axons are directed by chemical and physical signals toward a myriad of target cells. According to current dogma, the resulting network architecture is critically shaped by electrical interconnections, the synapses; however, key mechanisms translating neuronal interactions into neuronal growth behavior during network formation are still unresolved. To elucidate these mechanisms, we examined neurons interfacing nanopatterned substrates and compared them to natural interneuron interactions. We grew similar neuronal populations under three connectivity conditions, (1) the neurons are isolated, (2) the neurons are interconnected, and (3) the neurons are connected only to artificial substrates, then quantitatively compared both the cell morphologies and the transcriptome-expression profiles. Our analysis shows that whereas axon-guidance signaling pathways in isolated neurons are predominant, in isolated neurons interfacing nanotopography, these pathways are downregulated, similar to the interconnected neurons. Moreover, in nanotopography, interfacing neuron genes related to synaptogenesis and synaptic regulation are highly expressed, that is, again resembling the behavior of interconnected neurons. These molecular findings demonstrate that interactions with nanotopographies, although not leading to electrical coupling, play a comparable functional role in two major routes, neuronal guidance and network formation, with high relevance to the design of regenerative interfaces.

KEYWORDS:

Neuronal growth; RNA-sequencing; brain machine interface; gene expression; nanotopography

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