Generation and manipulation of magnetic multicellular spheroids

Multicellular spheroids have important applications in tumour studies, drug screening and tissue engineering. To enable simple manipulation of spheroids, magnetically labelled HeLa cells were cultured in hanging drops to generate magnetic spheroids. HeLa cells were labelled by biotinylating their cell membrane proteins and then binding streptavidin paramagnetic particles onto the biotinylated cell surface. Spheroids of different sizes were obtained by varying the seeding cell concentrations within the hanging drops and the spheroids had good cell viability. Characterisation of the F-actin distribution within the spheroids indicated a three dimensional reorganisation of the cellular cytoskeleton compared to monolayer cultures. The magnetic moment of the spheroids was measured and showed a superparamagnetic response in an applied field. Transmission electron microscopy analysis indicated that the paramagnetic particles were still present in the spheroids even after 21 days of culture. These spheroids could be easily and quickly separated magnetically without the need for centrifugation. The magnetic spheroids were also successfully manipulated and patterned using magnetic fields within a few seconds. The patterned spheroids then fused together to form a larger tissue construct.