A proteomic analysis of the interactions between poly(L-lactic acid) nanofibers and SH-SY5Y neuronal-like cells

Ana Marote; Nathalie Barroca; Rui Vitorino; Raquel M. Silva; Maria H.V. Fernandes; Paula M. Vilarinho; Odete A.B. da Cruz e Silva; Sandra I. Vieira; Ana Marote; Nathalie Barroca; Rui Vitorino; Raquel M. Silva; Maria H.V. Fernandes; Paula M. Vilarinho; Odete A.B. da Cruz e Silva; Sandra I. Vieira

doi:10.3934/molsci.2016.4.661

AIMS Molecular Science

2016, Volume 3, Issue 4: 661-682. doi: 10.3934/molsci.2016.4.661

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A proteomic analysis of the interactions between poly(L-lactic acid) nanofibers and SH-SY5Y neuronal-like cells

1.
iBIMED—Institute for Biomedicine, Department of Medical Sciences, Universidade de Aveiro, 3810-193 Aveiro, Portugal
2.
CICECO—Centre for Research in Ceramics and Composite Materials, Department of Materials and Ceramic Engineering, Universidade de Aveiro, 3810-193 Aveiro, Portugal
3.
QOPNA—Organic Chemistry, Natural Products and Food Stuffs, QOPNA, Universidade de Aveiro, 3810-193 Aveiro, Portugal
4.
iEETA—Institute of Electronics and Informatics Engineering of Aveiro, Universidade de Aveiro, 3810-193 Aveiro, Portugal

Received: 09 September 2016 Accepted: 06 November 2016 Published: 14 November 2016

Poly (L-lactic acid) (PLLA) is a biodegradable and biocompatible polymer that has been put forward as a promising material for therapeutic approaches aiming to restore neuronal function. The topographic cues present in PLLA-based scaffolds, defined by the technique used in their preparation, have been shown to play a role on the cellular behavior of adherent cells. Even though this interaction has been shown to influence the regenerative output of the scaffold, there is a lack of studies addressing this response at the proteomic level. Hence, this work focuses on the effect of electrospun PLLA-based nanofibers on the proteome, cellular processes and signaling pathways of SH-SY5Y neuroblastoma cells. It also further explores how these molecular mediators might influence cell proliferation and differentiation upon in vitro culture. For that, mass spectrometry followed by bioinformatics analysis was firstly performed and further complemented with Western blot, cell viability and imaging assays. Results show that PLLA nanofibers differentially activate and inhibit specific cellular functions and signaling pathways related to cell division, apoptosis, actin remodeling, among others. These ultimately block cellular proliferation and induce morphological rearrangements through cytoskeleton remodeling, adaptations that turn cells more prone to differentiate. In synthesis, PLLA nanofibers shift the SH-SY5Y cells proteome towards a state more responsive to differentiation-inductive cues such as the retinoic acid. Unveiling cells responses to nanomaterials is an important step to increase the tools available for their manipulation and potentiate their use in neural tissue engineering. Further studies should be performed to compare the effects of other topographic cues on cellular behavior.
- poly (L-lactic) acid scaffolds; nanofibers; cellular adaptation to nanomaterials; neuroregeneration; signaling for neuronal differentiation
Citation: Ana Marote, Nathalie Barroca, Rui Vitorino, Raquel M. Silva, Maria H.V. Fernandes, Paula M. Vilarinho, Odete A.B. da Cruz e Silva, Sandra I. Vieira. A proteomic analysis of the interactions between poly(L-lactic acid) nanofibers and SH-SY5Y neuronal-like cells[J]. AIMS Molecular Science, 2016, 3(4): 661-682. doi: 10.3934/molsci.2016.4.661

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Abstract

Poly (L-lactic acid) (PLLA) is a biodegradable and biocompatible polymer that has been put forward as a promising material for therapeutic approaches aiming to restore neuronal function. The topographic cues present in PLLA-based scaffolds, defined by the technique used in their preparation, have been shown to play a role on the cellular behavior of adherent cells. Even though this interaction has been shown to influence the regenerative output of the scaffold, there is a lack of studies addressing this response at the proteomic level. Hence, this work focuses on the effect of electrospun PLLA-based nanofibers on the proteome, cellular processes and signaling pathways of SH-SY5Y neuroblastoma cells. It also further explores how these molecular mediators might influence cell proliferation and differentiation upon in vitro culture. For that, mass spectrometry followed by bioinformatics analysis was firstly performed and further complemented with Western blot, cell viability and imaging assays. Results show that PLLA nanofibers differentially activate and inhibit specific cellular functions and signaling pathways related to cell division, apoptosis, actin remodeling, among others. These ultimately block cellular proliferation and induce morphological rearrangements through cytoskeleton remodeling, adaptations that turn cells more prone to differentiate. In synthesis, PLLA nanofibers shift the SH-SY5Y cells proteome towards a state more responsive to differentiation-inductive cues such as the retinoic acid. Unveiling cells responses to nanomaterials is an important step to increase the tools available for their manipulation and potentiate their use in neural tissue engineering. Further studies should be performed to compare the effects of other topographic cues on cellular behavior.

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