Oriented, Multimeric Biointerfaces of the L1 Cell Adhesion Molecule: An Approach to Enhance Neuronal and Neural Stem Cell Functions on 2-D and 3-D Polymer Substrates

Biointerphases

article

Jocie F. Cherry¹  Aaron L. Carlson¹  Farah L. Benarba¹  Sven D. Sommerfeld²  Devendra Verma¹  Gabriele Loers³  Joachim Kohn²  Melitta Schachner⁴  Prabhas V. Moghe⁵ 

[1] Department of Biomedical Engineering, Rutgers University;New Jersey Center for Biomaterials and Department of Chemistry and Chemical Biology, Rutgers University;Zentrum für Molekulare Neurobiologie, Universität Hamburg;W.M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University;Department of Biomedical Engineering and Department of Chemical and Biochemical Engineering, Rutgers University

关键词: Neurite Outgrowth;    Neuronal Differentiation;    Neural Cell Adhesion Molecule;    Polymer Thin Film;    Neurite Length;   

DOI  :  10.1007/s13758-012-0022-1

学科分类：基础医学

来源: SpringerOpen

【 摘 要 】

This article focuses on elucidating the key presentation features of neurotrophic ligands at polymer interfaces. Different biointerfacial configurations of the human neural cell adhesion molecule L1 were established on two-dimensional films and three-dimensional fibrous scaffolds of synthetic tyrosine-derived polycarbonate polymers and probed for surface concentrations, microscale organization, and effects on cultured primary neurons and neural stem cells. Underlying polymer substrates were modified with varying combinations of protein A and poly-d-lysine to modulate the immobilization and presentation of the Fc fusion fragment of the extracellular domain of L1 (L1-Fc). When presented as an oriented and multimeric configuration from protein A-pretreated polymers, L1-Fc significantly increased neurite outgrowth of rodent spinal cord neurons and cerebellar neurons as early as 24 h compared to the traditional presentation via adsorption onto surfaces treated with poly-d-lysine. Cultures of human neural progenitor cells screened on the L1-Fc/polymer biointerfaces showed significantly enhanced neuronal differentiation and neuritogenesis on all protein A oriented substrates. Notably, the highest degree of βIII-tubulin expression for cells in 3-D fibrous scaffolds were observed in protein A oriented substrates with PDL pretreatment, suggesting combined effects of cell attachment to polycationic charged substrates with subcellular topography along with L1-mediated adhesion mediating neuronal differentiation. Together, these findings highlight the promise of displays of multimeric neural adhesion ligands via biointerfacially engineered substrates to “cooperatively” enhance neuronal phenotypes on polymers of relevance to tissue engineering.

【 授权许可】

CC BY