Time-dependent active force drives periodic reversal in collective cell migration.

Biophys J

Laboratory for Multiscale Mechanics and Medical Science, Department of Engineering Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace Engineering, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Published: August 2025


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Article Abstract

Collective cell migration is prevalent in the processes of embryo development, wound healing, and cancer metastasis across various space and time scales. Although various motion modes have been identified, their relationships with single-cell motility and the underlying mechanisms remain poorly understood. In this study, we develop an active vertex model to investigate the spatiotemporal behavior of collective cells confined in annulus domain, accounting for the polarity memory effect of individual cells and the impact of confinement size. We reveal that cells spontaneously undergo periodic reversals in the rotation direction, with the inner boundary acting as the origin of initiation. The polarity delay with velocity and the growth of passive forces contribute to the reversals. The reversal frequency increases with the memory decay rate while remaining largely insensitive to the activity strength. In addition, we propose a polar order parameter to characterize various motion modes across a wide range of parameter spaces. This parameter effectively identifies four distinct dynamic regimes: global rotation, periodic reversal, oscillation, and local swirling. Our findings establish a framework for understanding the persistence of collective cell migration under geometric confinements and underscore the timescale required for molecular rearrangements during polarization.

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http://dx.doi.org/10.1016/j.bpj.2025.08.011DOI Listing

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