Person:

Needleman, Daniel

The proper positioning of mitotic spindle in the single-cell Caenorhabditis elegans embryo is achieved initially by the migration and rotation of the pronuclear complex (PNC) and its two associated astral microtubules (MTs). Pronuclear migration produces global cytoplasmic flows that couple the mechanics of all MTs, the PNC, and the cell periphery with each other through their hydrodynamic interactions (HIs). We present the first computational study that explicitly accounts for detailed HIs between the cytoskeletal components and demonstrate the key consequences of HIs for the mechanics of pronuclear migration. First, we show that, because of HIs between the MTs, the cytoplasm-filled astral MTs behave like a porous medium, with its permeability decreasing with increasing the number of MTs. We then directly study the dynamics of PNC migration under various force-transduction models, including the pushing or pulling of MTs at the cortex and the pulling of MTs by cytoplasmically bound force generators. Although achieving proper position and orientation on reasonable time scales does not uniquely choose a model, we find that each model produces a different signature in its induced cytoplasmic flow. We suggest that cytoplasmic flows can be used to differentiate between mechanisms.

Cytoskeletal networks are foundational examples of active matter and central to self-organized structures in the cell. In vivo, these networks are active and densely crosslinked. Relating their large-scale dynamics to the properties of their constituents remains an unsolved problem. Here, we study an in vitro active gel made from aligned microtubules and XCTK2 kinesin motors. Using photobleaching, we demonstrate that the gel’s aligned microtubules, driven by motors, continually slide past each other at a speed independent of the local microtubule polarity and motor concentration. This phenomenon is also observed, and remains unexplained, in spindles. We derive a general framework for coarse graining microtubule gels crosslinked by molecular motors from microscopic considerations. Using microtubule–microtubule coupling through a force–velocity relationship for kinesin, this theory naturally explains the experimental results: motors generate an active strain rate in regions of changing polarity, which allows microtubules of opposite polarities to slide past each other without stressing the material.