title: Accelerating bioelectric functional development of neural stem cells by graphene coupling: Implications for neural interfacing with conductive materials.
abstract: In order to govern cell-specific behaviors in tissue engineering for neural repair and regeneration, a better understanding of material-cell interactions, especially the bioelectric functions, is extremely important. Graphene has been reported to be a potential candidate for use as a scaffold and neural interfacing material. However, the bioelectric evolvement of cell membranes on these conductive graphene substrates remains largely uninvestigated. In this study, we used a neural stem cell (NSC) model to explore the possible changes in membrane bioelectric properties - including resting membrane potentials and action potentials - and cell behaviors on graphene films under both proliferation and differentiation conditions. We used a combination of single-cell electrophysiological recordings and traditional cell biology techniques. Graphene did not affect the basic membrane electrical parameters (capacitance and input resistance), but resting membrane potentials of cells on graphene substrates were more strongly negative under both proliferation and differentiation conditions. Also, NSCs and their progeny on graphene substrates exhibited increased firing of action potentials during development compared to controls. However, graphene only slightly affected the electric characterizations of mature NSC progeny. The modulation of passive and active bioelectric properties on the graphene substrate was accompanied by enhanced NSC differentiation. Furthermore, spine density, synapse proteins expressions and synaptic activity were all increased in graphene group. Modeling of the electric field on conductive graphene substrates suggests that the electric field produced by the electronegative cell membrane is much higher on graphene substrates than that on control, and this might explain the observed changes of bioelectric development by graphene coupling. Our results indicate that graphene is able to accelerate NSC maturation during development, especially with regard to bioelectric evolvement. Our findings provide a fundamental understanding of the role of conductive materials in tuning the membrane bioelectric properties in a graphene model and pave the way for future studies on the development of methods and materials for manipulating membrane properties in a controllable way for NSC-based therapies.
authors: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors: Rongrong
authors: R
authors: Guo
authors: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors: Shasha
authors: S
authors: Zhang
authors: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors: Miao
authors: M
authors: Xiao
authors: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors: Fuping
authors: F
authors: Qian
authors: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors: Zuhong
authors: Z
authors: He
authors: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors: Dan
authors: D
authors: Li
authors: Department of Otolaryngology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors: Xiaoli
authors: X
authors: Zhang
authors: Department of Otorhinolaryngology, Hearing Research Institute, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, 200031, China.
authors: Huawei
authors: H
authors: Li
authors: School of Materials Science and Engineering, Tongji University, Shanghai 201804, China.
authors: Xiaowei
authors: X
authors: Yang
authors: CAS Key Laboratory of Brain Function and Diseases and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Ming
authors: M
authors: Wang
authors: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: renjiec@seu.edu.cn.
authors: Renjie
authors: R
authors: Chai
authors: Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: mingliangtang@seu.edu.cn.
authors: Mingliang
authors: M
authors: Tang
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000737:chemistry*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003198:Computer Simulation; D004553:Electric Conductivity; D017097:Electric Impedance; D004566:Electrodes; D006108:Graphite / Q000737:chemistry*; D008422:Materials Testing; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D006108:Graphite
keywords: Bioelectric properties; Differentiation; Graphene; Neural stem cells