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Neufeld, Z.

Publications and source records attributed to Neufeld, Z..

3 recordsLinked to original sources

Processivity of molecular motors under vectorial loads

Molecular motors are cellular machines that drive the spatial organisation of the cells by transporting cargoes along intracellular filaments. Although the mechanical properties of single molecular motors are relatively well characterised, it remains elusive how the three-dimensional 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 analysing the load-dependence of the stepping and detachment processes. We find that the processivity of kinesin increases with lowering the load angle between kinesin and 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.

biophysics

Theoretical analysis of neural crest cell migration

The neural crest cells are embryonic stem cells that migrate throughout embryos and, at different target locations, give rise to the formation of a variety of tissues and organs. The directional migration of the neural crest cells is experimentally described using a process referred to as contact inhibition of locomotion (CIL), by which cells redirect their movement upon the cell-cell contacts. However, it is unclear how the migration alignment is affected by the motility properties of the cells. Here, we computationally model the migration alignment and the average time to reach a target location as functions of the motility dynamics and interaction of the cells in an open domain with a channel geometry. The results indicate that by varying the properties of the CIL interaction a transition takes place from random movement of the cells to an organized collective migration, where the migration alignment is maximised and the migration time is minimised. This phase transition is accelerated and strengthened with the influx rate of the cells into the domain through increasing the density of the migrating cells. The model further suggests that the migration is more coordinated when the cells with a large CIL radius move fast in a narrow domain.

biophysics

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.

biophysics