Contractile ring composition dictates kinetics of in silico contractility

Constriction kinetics of the cytokinetic ring are expected to depend on dynamic adjustment of contractile ring composition, but the impact of ring component abundance dynamics on ring constriction is understudied. Computational models generally assume that contractile networks maintain constant total amounts of components, which is not always true. To test how compositional dynamics affect constriction kinetics, we first measured F-actin, non-muscle myosin II, septin, and anillin dur-ing Caenorhabditis elegans zygotic mitosis. A custom microfluidic device that positioned the cell with the division plane parallel to a light sheet allowed even illumination of the cytokinetic ring. Measured component abundances were implemented in a three-dimensional agent-based model of a membrane-associated contractile ring. With constant network component amounts, constriction completed with biologically unrealistic kinetics. However, imposing the measured changes in component quantities allowed this model to elicit realistic constriction kinetics. Simulated networks were more sensitive to changes in motor and filament amounts than those of crosslinkers and tethers. Our findings highlight the importance of network composition for actomyosin contraction kinetics.SIGNIFICANCE We created a microfluidic device compatible with high-numerical-aperture light-sheet microscopy to measure cytokinetic ring component abundance during cytokinesis in the Caenorhabditis elegans zygote. Implementing measured dynamics into our three-dimensional agent-based model of a contractile ring elicited biologically realistic kinetics. This work enhances our understanding of factors that affect contractile force generation during cytokinesis, and highlights the importance of component abundance for proper constriction kinetics. Of specific importance to constriction is motor filament abundance, which directly leads to more accurate representation of biological kinetics.

Automated summary

In this study, the researchers used a microfluidic device and high-numerical-aperture light-sheet microscopy to measure the dynamic changes in cytokinetic ring component abundance. They implemented the measured data into a model and observed biologically realistic cytokinetic kinetics. The findings emphasize the importance of network composition, particularly motor filament abundance, for actomyosin contraction kinetics.