  Cell spheroids are a widely used model to investigate cell-cell and
cell-matrix interactions in a 3D microenvironment in vitro. Most research on
cell spheroids has been focused on their response to various stimuli under
static conditions. Recently, the effect of flow on cell spheroids has been
investigated in the context of tumor invasion in interstitial space. In
particular, microfluidic perfusion of cell spheroids embedded in a collagen
matrix has been shown to modulate cell-cell adhesion and to represent a
possible mechanism promoting tumor invasion by interstitial flow. However,
studies on the effects of well-defined flow fields on cell spheroids are
lacking in the literature. Here, we apply simple shear flow to cell spheroids
in a parallel plate apparatus while observing their morphology by optical
microscopy. By using image analysis techniques, we show that cell spheroids
rotate under flow as rigid particles. As time goes on, cells from the outer
layer detach from the sheared cell spheroids and are carried away by the flow.
Hence, the size of cell spheroids declines with time at a rate increasing with
the external shear stress, which can be used to estimate cell-cell adhesion.
The technique proposed in this work allows one to correlate flow-induced
effects with microscopy imaging of cell spheroids in a well-established shear
flow field, thus providing a method to obtain quantitative results which are
relevant in the general field of mechanobiology.
