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Living systems exhibit self-organization, a phenomenon that enables organisms to perform functions essential for life. The interior of living cells is a crowded environment in which the self-assembly of cytoskeletal networks is spatially constrained by membranes and organelles. Cytoskeletal filaments undergo active condensation in the presence of crosslinking motor proteins. In past studies, confinement has been shown to alter the morphology of active condensates. Here, we perform simulations to explore systems of filaments and crosslinking motors in a variety of confining geometries. We simulate spatial confinement imposed by hard spherical, cylindrical, and planar boundaries. These systems exhibit non-equilibrium condensation behavior where crosslinking motors condense a fraction of the overall filament population, leading to coexistence of vapor and condensed states. We find that the confinement lengthscale modifies the dynamics and condensate morphology. With end-pausing crosslinking motors, filaments self-organize into half asters and fully-symmetric asters under spherical confinement, polarity-sorted bilayers and bottle-brush-like states under cylindrical confinement, and flattened asters under planar confinement. The number of crosslinking motors controls the size and shape of condensates, with flattened asters becoming hollow and ring-like for larger motor number. End pausing plays a key role affecting condensate morphology: systems with end-pausing motors evolve into aster-like condensates while those with non-end-pausing crosslinking motor proteins evolve into disordered clusters and polarity-sorted bundles. 

The cytoskeleton – a collection of polymeric filaments, molecular motors, and crosslinkers – is a foundational example of active matter, and in the cell assembles into organelles that guide basic biological functions. Simulation of cytoskeletal assemblies is an important tool for modeling cellular processes and understanding their surprising material properties. Here, we present aLENS (a Living Ensemble Simulator), a novel computational framework designed to surmount the limits of conventional simulation methods. We model molecular motors with crosslinking kinetics that adhere to a thermodynamic energy landscape, and integrate the system dynamics while efficiently and stably enforcing hard-body repulsion between filaments. Molecular potentials are entirely avoided in imposing steric constraints. Utilizing parallel computing, we simulate tens to hundreds of thousands of cytoskeletal filaments and crosslinking motors, recapitulating emergent phenomena such as bundle formation and buckling. This simulation framework can help elucidate how motor type, thermal fluctuations, internal stresses, and confinement determine the evolution of cytoskeletal active matter. 

The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood, despite extensive study. To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle, we developed a computational model of fission-yeast mitosis. Robust chromosome biorientation requires progressive restriction of attachment geometry, destabilization of misaligned attachments, and attachment force dependence. Large spindle length fluctuations can occur when the kinetochore-microtubule attachment lifetime is long. The primary spindle force generators are kinesin-5 motors and crosslinkers in early mitosis, while interkinetochore stretch becomes important after biorientation. The same mechanisms that contribute to persistent biorientation lead to segregation of chromosomes to the poles after anaphase onset. This model therefore provides a framework to interrogate key requirements for robust chromosome biorientation, spindle length regulation, and force generation in the spindle.