Matrix molecules convey biochemical and physical guiding signals to neurons in the central nervous system (CNS) and shape the trajectory of neuronal fibers that constitute neural networks. We have developed recombinant human IgMs that bind to epitopes on neural cells, with the aim of treating neurological diseases. Here we test the hypothesis that recombinant human IgMs (rHIgM) can guide neurite outgrowth of CNS neurons. Microcontact printing was employed to pattern rHIgM12 and rHIgM22, antibodies that were bioengineered to have variable regions capable of binding to neurons or oligodendrocytes, respectively. rHIgM12 promoted neuronal attachment and guided outgrowth of neurites from hippocampal neurons. Processes from spinal neurons followed grid patterns of rHIgM12 and formed a physical network. Comparison between rHIgM12 and rHIgM22 suggested the biochemistry that facilitates anchoring the neuronal surfaces is a prerequisite for the function of IgM, and spatial properties cooperate in guiding the assembly of neuronal networks.
Bibliographical noteFunding Information:
This work was supported by grants from the NIH (R01 GM092993, R01 NS048357 and R21 NS073684), the National Science Foundation CAREER Award (DBI 1054191), the Minnesota Partnership Award for Biotechnology and Medical Genomics, and the National Multiple Sclerosis Society (CA 1060A). This work was also supported by a High-Impact Pilot and Feasibility Award (HIPFA) and Novel Methodology Award (NMDA) from the Mayo Clinic Center for Translational Science Activities (CTSA) and Mayo Clinic CTSA grant number UL1 TR000135 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). We also acknowledge with thanks support from the Applebaum, Hilton, Peterson and Sanford Foundations.