Quantitating Cell–Cell Interaction Functions with Applications to Glioblastoma Multiforme Cancer Cells

We report on a method for quantitating the distance dependence of cell–cell interactions. We employ a microchip design that permits a multiplex, quantitative protein assay from statistical numbers of cell pairs, as a function of cell separation, with a 0.15 nL volume microchamber. We interrogate interactions between pairs of model brain cancer cells by assaying for six functional proteins associated with PI3k signaling. At short incubation times, cells do not appear to influence each other, regardless of cell separation. For 6 h incubation times, the cells exert an inhibiting influence on each other at short separations and a predominately activating influence at large separation. Protein-specific cell–cell interaction functions are extracted, and by assuming pairwise additivity of those interactions, the functions are shown to correctly predict the results from three-cell experiments carried out under the identical conditions.