title: Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures.
abstract: The ability to construct easily in vitro networks of primary neurons organized with imposed topologies is required for neural tissue engineering as well as for the development of neuronal interfaces with desirable characteristics. However, accumulating evidence suggests that the mechanical properties of the culture matrix can modulate important neuronal functions such as growth, extension, branching and activity. Here we designed robust and reproducible laminin-polylysine grid micropatterns on cell culture substrates that have similar biochemical properties but a 100-fold difference in Young's modulus to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks. We found that cell bodies of primary cortical neurons gradually accumulate in circular islands, whereas axonal extensions spread on linear tracks to connect circular islands. Our findings indicate that migration of cortical neurons is enhanced on soft substrates, leading to a faster formation of neuronal networks. Furthermore, the pre-synaptic density was two times higher on stiff substrates and consistently the number of action potentials and miniature synaptic currents was enhanced on stiff substrates. Taken together, our results provide compelling evidence to indicate that matrix stiffness is a key parameter to modulate the growth dynamics, synaptic density and electrophysiological activity of cortical neuronal networks, thus providing useful information on scaffold design for neural tissue engineering.
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Joséphine
authors.initials: J
authors.lastname: Lantoine
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grevesse
authors.affiliation: Department of Neuroscience, University of Mons, Belgium.
authors.forename: Agnès
authors.initials: A
authors.lastname: Villers
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Delhaye
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Camille
authors.initials: C
authors.lastname: Mestdagh
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Versaevel
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Danahe
authors.initials: D
authors.lastname: Mohammed
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Bruyère
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Alaimo
authors.affiliation: Laboratory for Soft Bioelectronics Interfaces, Centre for Neuroprosthetics, Ecole Fédérale Polytechnique de Lausanne, Switzerland.
authors.forename: Stéphanie P
authors.initials: SP
authors.lastname: Lacour
authors.affiliation: Department of Neuroscience, University of Mons, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ris
authors.affiliation: Mechanobiology & Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium. Electronic address: sylvain.gabriele@umons.ac.be.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gabriele
mesh_terms: D000200:Action Potentials; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002465:Cell Movement; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology*; D055119:Elastic Modulus; D007797:Laminin / Q000737:chemistry*; D009415:Nerve Net / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D011107:Polylysine / Q000737:chemistry*; D051381:Rats; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D007797:Laminin; D011107:Polylysine
keywords: Matrix stiffness; Mechanotaxis; Micropatterning; Migration; Neuronal networks