title: Stiff substrates enhance cultured neuronal network activity.
abstract: The mechanical property of extracellular matrix and cell-supporting substrates is known to modulate neuronal growth, differentiation, extension and branching. Here we show that substrate stiffness is an important microenvironmental cue, to which mouse hippocampal neurons respond and integrate into synapse formation and transmission in cultured neuronal network. Hippocampal neurons were cultured on polydimethylsiloxane substrates fabricated to have similar surface properties but a 10-fold difference in Young's modulus. Voltage-gated Ca(2+) channel currents determined by patch-clamp recording were greater in neurons on stiff substrates than on soft substrates. Ca(2+) oscillations in cultured neuronal network monitored using time-lapse single cell imaging increased in both amplitude and frequency among neurons on stiff substrates. Consistently, synaptic connectivity recorded by paired recording was enhanced between neurons on stiff substrates. Furthermore, spontaneous excitatory postsynaptic activity became greater and more frequent in neurons on stiff substrates. Evoked excitatory transmitter release and excitatory postsynaptic currents also were heightened at synapses between neurons on stiff substrates. Taken together, our results provide compelling evidence to show that substrate stiffness is an important biophysical factor modulating synapse connectivity and transmission in cultured hippocampal neuronal network. Such information is useful in designing instructive scaffolds or supporting substrates for neural tissue engineering.
authors.affiliation: 1] Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, China [2] College of Mechanics, Taiyuan University of Technology, China [3].
authors.forename: Quan-You
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: 1] Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, China [2].
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Medical School, Datong University, China.
authors.forename: Chen-Xu
authors.initials: CX
authors.lastname: Li
authors.affiliation: College of Mechanics, Taiyuan University of Technology, China.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, China.
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, China.
authors.forename: Xiao-an
authors.initials: XA
authors.lastname: Wu
authors.affiliation: Biomechanics and Biomaterials Laboratory, Department of Applied Mechanics, School of Aerospace Engineering, Beijing Institute of Technology, China.
authors.forename: Shu-Na
authors.initials: SN
authors.lastname: Li
authors.affiliation: Biomechanics and Biomaterials Laboratory, Department of Applied Mechanics, School of Aerospace Engineering, Beijing Institute of Technology, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huo
authors.affiliation: 1] School of Biomedical Sciences, University of Leeds, United Kingdom [2] Department of Physiology and Neurobiology, School of Basic Medical Sciences, Xinxiang Medical University, China.
authors.forename: Lin-Hua
authors.initials: LH
authors.lastname: Jiang
authors.affiliation: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, China.
authors.forename: Hu-Cheng
authors.initials: HC
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D003470:Culture Media; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats
chemical_list: D015220:Calcium Channels; D003470:Culture Media