Modulation of oligodendrocyte differentiation and maturation by combined biochemical and mechanical cues

• Published in: Scientific reports Vol. 6; no. 1; p. 21563
• Main Authors: Lourenço, Tânia, Paes de Faria, Joana, Bippes, Christian A., Maia, João, Lopes-da-Silva, José A., Relvas, João B., Grãos, Mário
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.02.2016; Nature Publishing Group
• Subjects: 13/1; 13/51; 14/34; 14/63; 631/1647/245/2225; 631/378/2596/1705; 631/57; 631/80; 82/29; Acrylic Resins - chemistry; Animals; Biomechanical Phenomena; Cell culture; Cell Differentiation; Cell Line; Cell proliferation; Central nervous system; Extracellular matrix; Extracellular Matrix - physiology; Fibronectin; Fibronectins - metabolism; Glial stem cells; Humanities and Social Sciences; Laminin - metabolism; Manganese; Mechanical properties; multidisciplinary; Myelin; Myelin basic protein; Myelin Basic Protein - metabolism; Myelin proteolipid protein; Myelin Proteolipid Protein - metabolism; Oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - physiology; Proteins; Rats; Rigidity; Rodents; Science; Substrates
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep21563

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.