title: Modulation of oligodendrocyte differentiation and maturation by combined biochemical and mechanical cues.
abstract: Extracellular matrix (ECM) proteins play a key role during oligodendrogenesis. While fibronectin (FN) is involved in the maintenance and proliferation of oligodendrocyte progenitor cells (OPCs), merosin (MN) promotes differentiation into oligodendrocytes (OLs). Mechanical properties of the ECM also seem to affect OL differentiation, hence this study aimed to clarify the impact of combined biophysical and biochemical elements during oligodendrocyte differentiation and maturation using synthetic elastic polymeric ECM-like substrates. CG-4 cells presented OPC- or OL-like morphology in response to brain-compliant substrates functionalised with FN or MN, respectively. The expression of the differentiation and maturation markers myelin basic protein--MBP--and proteolipid protein--PLP--(respectively) by primary rat oligodendrocytes was enhanced in presence of MN, but only on brain-compliant conditions, considering the distribution (MBP) or amount (PLP) of the protein. It was also observed that maturation of OLs was attained earlier (by assessing PLP expression) by cells differentiated on MN-functionalised brain-compliant substrates than on standard culture conditions. Moreover, the combination of MN and substrate compliance enhanced the maturation and morphological complexity of OLs. Considering the distinct degrees of stiffness tested ranging within those of the central nervous system, our results indicate that 6.5 kPa is the most suitable rigidity for oligodendrocyte differentiation.
authors.affiliation: Biocant, Technology Transfer Association, Cantanhede, Portugal.|Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Lourenço
authors.affiliation: IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.|i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Paes de Faria
authors.affiliation: Nanosurf AG, Liestal, Switzerland.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Bippes
authors.affiliation: Chemical Engineering Department, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Maia
authors.affiliation: QOPNA, Chemistry Department, University of Aveiro, Aveiro, Portugal.
authors.forename: José A
authors.initials: JA
authors.lastname: Lopes-da-Silva
authors.affiliation: IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.|i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: João B
authors.initials: JB
authors.lastname: Relvas
authors.affiliation: Biocant, Technology Transfer Association, Cantanhede, Portugal.|Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Grãos
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D002460:Cell Line; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D051381:Rats
chemical_list: D000180:Acrylic Resins; D005353:Fibronectins; D007797:Laminin; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; C016680:polyacrylamide gels