Force generated by two kinesin motors depends on the load direction and intermolecular coupling

Kinesins are molecular motors that carry cellular cargoes. While the mechanics of single kinesins are well characterized experimentally, the behavior of multiple kinesins varies considerably among experiments. The basis for this variability is unknown. Here, we resolve single-motor force measurements into a vertical component, which accelerates kinesin detachment, and a horizontal component, which decelerates the detachment when resisting the motor. This directionality, when the different experimental geometries are considered, can account for much of the variation in multiple motor dynamics

Multiscale modelling of motility wave propagation in cell migration

The collective motion of cell monolayers within a tissue is a fundamental biological process that occurs during tissue formation, wound healing, cancerous invasion, and viral infection. Experiments have shown that at the onset of migration, the motility is self-generated as a polarization wave starting from the leading edge of the monolayer and progressively propagates into the bulk. However, it is unclear how the propagation of this motility wave is influenced by cellular properties. Here, we investigate this using a computational model based on the Potts model coupled to the dynamics of intracellular polarization. The model captures the propagation of the polarization wave initiated at the leading edge and suggests that the cells cortex can regulate the migration modes: strongly contractile cells may depolarize the monolayer, whereas less contractile cells can form swirling movement. Cortical contractility is further found to limit the cells motility, which (i) decelerates the wave speed and the leading edge progression, and (ii) destabilises the leading edge into migration fingers. Together, our model describes how different cellular properties can contribute to the regulation of collective cell migration

Processivity of molecular motors under vectorial loads

Molecular motors are cellular machines that drive the spatial organization of the cells by transporting cargos along intracellular filaments. Although the mechanical properties of single molecular motors are relatively well characterized, it remains elusive how the geometry of a load imposed on a motor affects its processivity, i.e., the average distance that a motor moves per interaction with a filament. Here, we theoretically explore this question for a single-kinesin molecular motor by analyzing the load dependence of the stepping and detachment processes. We find that the processivity of the kinesin increases with lowering the load angle between the kinesin and the microtubule filament, due to the deceleration of the detachment rate. When the load angle is large, the processivity is predicted to enhance with accelerating the stepping rate through an optimal distribution of the load over the kinetic transition rates underlying a mechanical step of the motor. These results provide new insights into understanding of the design of potential synthetic biomolecular machines that can travel long distances with high velocities

Modelling of Tissue Invasion in Epithelial Monolayers

Mathematical and computational models are used to describe biomechanical processes in multicellular systems. Here, we develop a model to analyse how two types of epithelial cell layers interact during tissue invasion depending on their cellular properties, i.e., simulating cancer cells expanding into a region of normal cells. We model the tissue invasion process using the cellular Potts model and implement our two-dimensional computational simulations in the software package CompuCell3D. The model predicts that differences in mechanical properties of cells can lead to tissue invasion, even if the division rates and death rates of the two cell types are the same. We also show how the invasion speed varies depending on the cell division and death rates and the mechanical properties of the cells

Modelling of Tissue Invasion in Epithelial Monolayers

Mathematical and computational models are used to describe biomechanical processes in multicellular systems. Here, we develop a model to analyse how two types of epithelial cell layers interact during tissue invasion depending on their cellular properties, i.e., simulating cancer cells expanding into a region of normal cells. We model the tissue invasion process using the cellular Potts model and implement our two-dimensional computational simulations in the software package CompuCell3D. The model predicts that differences in mechanical properties of cells can lead to tissue invasion, even if the division rates and death rates of the two cell types are the same. We also show how the invasion speed varies depending on the cell division and death rates and the mechanical properties of the cells