(103b) Cell Surface Complexity Modulates Membrane Capacitance and Differentiation of Human Neural Stem Cells

Human neural stem cells have potential as therapeutic candidates for the treatment of a number of neurodegenerative diseases or neurotraumas. Important issues that need to be addressed to improve the utility of these cells in clinical trials include characterization of the heterogeneity in stem cell populations and ways to modulate cell differentiation. Our previous studies have shown differential membrane capacitance values for cells with astrogenic and neurogenic fate. In the present study we have investigated the modulatory effect of cell surface complexity on membrane capacitance and differentiation of these human neural stem cells.

Membrane capacitance was measured using the 3DEP analyzer, a microdevice that uses electric fields to quickly quantitate capacitance. The cell surface of human neural stem cells was altered by treating cells with N-acetylglucosamine (GlcNAc), which feeds into N-glycosylation pathways leading to the formation of complex, highly-branched sugars. Treatment of human neural stem cells with GlcNAc significantly increases complex branching on the cell surface (lectin LPHA, untreated 18485+/-2069 SEM mean fluorescence intensity (MFI), GlcNAc treated 40863 +/- 4428 SEM. MFI, p<0.001). Increasing complex branching on human neural stem cells significantly increases membrane capacitance (untreated 7.5 +/- 0.18 s.e.m. mF/m², GlcNAc treated 9.3 +/- 0.47 s.e.m. mF/m²; p<0.001)), showing that cell surface glycosylation patterns impact membrane capacitance values. Modulation of cell surface complexity also affects cell differentiation. Increase in cell surface N-glycosylation increases the percentage of cells expressing undifferentiated cell markers after the cells were in differentiation conditions. Taken together these results indicate a direct association between membrane capacitance, cell surface complexity and differentiation of human neural stem cells.