Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.

<h4>Background</h4>Recently, the effects of nanogratings have been investigated on PC12 with respect to cell polarity, neuronal differentiation, migration, maturation of focal adhesions and alignment of neurites.<h4>Methodology/principal findings</h4>A synergistic procedure w...

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Autores principales:	Pier Nicola Sergi, Iolanda Morana Roccasalvo, Ilaria Tonazzini, Marco Cecchini, Silvestro Micera
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96cf9d10bbeb48a5ba668ee6747e2c2f
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spelling	oai:doaj.org-article:96cf9d10bbeb48a5ba668ee6747e2c2f2021-11-18T09:01:01ZCell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.1932-620310.1371/journal.pone.0070304https://doaj.org/article/96cf9d10bbeb48a5ba668ee6747e2c2f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936404/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Recently, the effects of nanogratings have been investigated on PC12 with respect to cell polarity, neuronal differentiation, migration, maturation of focal adhesions and alignment of neurites.<h4>Methodology/principal findings</h4>A synergistic procedure was used to study the mechanism of alignment of PC12 neurites with respect to the main direction of nanogratings. Finite Element simulations were used to qualitatively assess the distribution of stresses at the interface between non-spread growth cones and filopodia, and to study their dependence on filopodial length and orientation. After modelling all adhesions under non-spread growth cone and filopodial protrusions, the values of local stress maxima resulted from the length of filopodia. Since the stress was assumed to be the main triggering cause leading to the increase and stabilization of filopodia, the position of the local maxima was directly related to the orientation of neurites. An analytic closed form equation was then written to quantitatively assess the average ridge width needed to achieve a given neuritic alignment (R(2) = 0.96), and the alignment course, when the ridge depth varied (R(2) = 0.97). A computational framework was implemented within an improved free Java environment (CX3D) and in silico simulations were carried out to reproduce and predict biological experiments. No significant differences were found between biological experiments and in silico simulations (alignment, p = 0.3571; tortuosity, p = 0.2236) with a standard level of confidence (95%).<h4>Conclusions/significance</h4>A mechanism involved in filopodial sensing of nanogratings is proposed and modelled through a synergistic use of FE models, theoretical equations and in silico simulations. This approach shows the importance of the neuritic terminal geometry, and the key role of the distribution of the adhesion constraints for the cell/substrate coupling process. Finally, the effects of the geometry of nanogratings were explicitly considered in cell/surface interactions thanks to the analytic framework presented in this work.Pier Nicola SergiIolanda Morana RoccasalvoIlaria TonazziniMarco CecchiniSilvestro MiceraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70304 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pier Nicola Sergi Iolanda Morana Roccasalvo Ilaria Tonazzini Marco Cecchini Silvestro Micera Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.
description	<h4>Background</h4>Recently, the effects of nanogratings have been investigated on PC12 with respect to cell polarity, neuronal differentiation, migration, maturation of focal adhesions and alignment of neurites.<h4>Methodology/principal findings</h4>A synergistic procedure was used to study the mechanism of alignment of PC12 neurites with respect to the main direction of nanogratings. Finite Element simulations were used to qualitatively assess the distribution of stresses at the interface between non-spread growth cones and filopodia, and to study their dependence on filopodial length and orientation. After modelling all adhesions under non-spread growth cone and filopodial protrusions, the values of local stress maxima resulted from the length of filopodia. Since the stress was assumed to be the main triggering cause leading to the increase and stabilization of filopodia, the position of the local maxima was directly related to the orientation of neurites. An analytic closed form equation was then written to quantitatively assess the average ridge width needed to achieve a given neuritic alignment (R(2) = 0.96), and the alignment course, when the ridge depth varied (R(2) = 0.97). A computational framework was implemented within an improved free Java environment (CX3D) and in silico simulations were carried out to reproduce and predict biological experiments. No significant differences were found between biological experiments and in silico simulations (alignment, p = 0.3571; tortuosity, p = 0.2236) with a standard level of confidence (95%).<h4>Conclusions/significance</h4>A mechanism involved in filopodial sensing of nanogratings is proposed and modelled through a synergistic use of FE models, theoretical equations and in silico simulations. This approach shows the importance of the neuritic terminal geometry, and the key role of the distribution of the adhesion constraints for the cell/substrate coupling process. Finally, the effects of the geometry of nanogratings were explicitly considered in cell/surface interactions thanks to the analytic framework presented in this work.
format	article
author	Pier Nicola Sergi Iolanda Morana Roccasalvo Ilaria Tonazzini Marco Cecchini Silvestro Micera
author_facet	Pier Nicola Sergi Iolanda Morana Roccasalvo Ilaria Tonazzini Marco Cecchini Silvestro Micera
author_sort	Pier Nicola Sergi
title	Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.
title_short	Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.
title_full	Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.
title_fullStr	Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.
title_full_unstemmed	Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.
title_sort	cell guidance on nanogratings: a computational model of the interplay between pc12 growth cones and nanostructures.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/96cf9d10bbeb48a5ba668ee6747e2c2f
work_keys_str_mv	AT piernicolasergi cellguidanceonnanogratingsacomputationalmodeloftheinterplaybetweenpc12growthconesandnanostructures AT iolandamoranaroccasalvo cellguidanceonnanogratingsacomputationalmodeloftheinterplaybetweenpc12growthconesandnanostructures AT ilariatonazzini cellguidanceonnanogratingsacomputationalmodeloftheinterplaybetweenpc12growthconesandnanostructures AT marcocecchini cellguidanceonnanogratingsacomputationalmodeloftheinterplaybetweenpc12growthconesandnanostructures AT silvestromicera cellguidanceonnanogratingsacomputationalmodeloftheinterplaybetweenpc12growthconesandnanostructures
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Cell guidance on nanogratings: a computational model of the interplay between PC12 growth cones and nanostructures.

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