Abstract
A controlled geometry of in vitro neuronal networks allows investigation of the cellular mechanisms that underlie neuron-to-neuron and neuron–extracellular matrix interactions, which are essential to biomedical research. Herein, we report a selective guidance of primary hippocampal neurons by using arrays of three-dimensional vertical nanopillars (NPs) functionalized with a specific adhesion-promoting molecule—poly-dl-ornithine (PDLO). We show that 90% of neuronal cells are guided exclusively on the combinatorial PDLO/NP substrate. Moreover, we demonstrate the influence of the interplay between nanostructures and neurons on synapse formation and maturation, resulting in increased expression of postsynaptic density-95 protein and enhanced network cellular activity conferred by the endogenous c-fos expression. Successful guidance to foster synapse stability and cellular activity on multilevel cues of surface topography and chemical functionalization suggests the potential to devise technologies to control neuronal growth on nanostructures for tissue engineering, neuroprostheses, and drug development.
Highlights
The function of the nervous system relies on the complex architecture of the extraordinary number of neuronal subtypes.[1]The complexity of human behaviors is determined by the coordination of globally integrated activity of neuronal ensembles, which is itself mediated by the activity-dependent changes in synaptic efficacy.[2]
This feature promotes the interaction between the cell membrane and PDLO/NPs because of the adaptation of NPs to forces exerted by cell attachment leading to tight adhesion rather than cell penetration.[40]
Our results demonstrate the ordering and alignment of neuronal ensembles provided by the combinatorial patterning effect of nanotopographical cues using 3D NPs and biochemical cues exerted by the PDLO
Summary
The function of the nervous system relies on the complex architecture of the extraordinary number of neuronal subtypes.[1]The complexity of human behaviors is determined by the coordination of globally integrated activity of neuronal ensembles, which is itself mediated by the activity-dependent changes in synaptic efficacy.[2]. Dysregulation of electrical and synaptic activities has been found in different neurological disorders.[4−6] In vivo, cellular responses such as proliferation, differentiation, migration, and apoptosis[7] are influenced by the competitive external biochemical and physical guidance cues in the neuronal microenvironment,[8] of which the extracellular matrix (ECM) is one of the main components.[9] the investigation of a defined set of physical and chemical neuronal guidance cues that foster synapse maturation and stability is essential but has remained so far incomplete It is of great interest in neuroscience, tissue engineering, and regenerative medicine to adopt a reductionist in vitro model implemented as artificial niches to understand multiple cellular mechanisms of cell-to-cell and cell signaling pathways. This model is essential to provide a better understanding of basic research studies and pathologies as well as investigating cellular responses for building neuroprosthetic scaffolds and drug development
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