Impact of Cell Shape on Mitotic Spindle Positioning Forces

Abstract

Cell geometry is a key parameter for the regulation of mitotic spindle positioning during early embryo development and tissue morphogenesis. To date, however, we still lack an understanding for how intracellular forces that position, orient or hold mitotic spindles depend on cell geometry. Here, we used in vivo magnetic tweezers to directly measure the forces that maintain the mitotic spindle in the center of sea urchin cells that adopt different shapes during early embryo development. We found that spindles are held by viscoelastic forces that progressively increase in amplitude as cells become more elongated during early development. By coupling direct cell shape manipulations and in vivo force measurements, we establish how spindle associated forces increase in dose dependence with cell shape anisotropy. Cytoplasm flow analysis and hydrodynamic simulations suggest that this geometry-dependent mechanical enhancement results from a stronger hydrodynamic coupling between the spindle and cell boundaries, which dampens cytoplasm flows and spindle mobility as cells become more elongated. These findings establish how cell shape affects spindle associated forces, and suggest a novel mechanism for shape-sensing and division positioning mediated by intracellular hydrodynamics with functional implications for early embryo morphogenesis.