Abstract
Collective cell migration is observed during morphogenesis, angiogenesis, and wound healing, and this type of cell migration also contributes to efficient metastasis in some kinds of cancers. Because collectively migrating cells are much better organized than a random assemblage of individual cells, there seems to be a kind of order in migrating clusters. Extensive research has identified a large number of molecules involved in collective cell migration, and these factors have been analyzed using dramatic advances in imaging technology. To date, however, it remains unclear how myriad cells are integrated as a single unit. Recently, we observed unbalanced collective cell migrations that can be likened to either precision dancing or awa-odori, Japanese traditional dancing similar to the style at Rio Carnival, caused by the impairment of the conformational change of JRAB/MICAL-L2. This review begins with a brief history of image-based computational analyses on cell migration, explains why quantitative analysis of the stylization of collective cell behavior is difficult, and finally introduces our recent work on JRAB/MICAL-L2 as a successful example of the multidisciplinary approach combining cell biology, live imaging, and computational biology. In combination, these methods have enabled quantitative evaluations of the “dancing style” of collective cell migration.
Highlights
Reviewed by: Thomas Fath, University of New South Wales, Australia Zhizhan Gu, Albert Einstein College of Medicine, United States
Collective cell migration is observed during morphogenesis, angiogenesis, and wound healing, and this type of cell migration contributes to efficient metastasis in some kinds of cancers
These observations indicate that at the front, the closed form of JRAB/MICAL-L2 plays a role in the generation of traction force that pulls the population in a certain direction, whereas the open form of JRAB/MICAL-L2 contributes to formation and maintenance of stable cell–cell adhesion between follower cells, enabling them to behave as a single unit
Summary
Cell migration is a fundamental cellular function involved in various biological processes. Motion analysis based on segmentation and tracking approaches has been often applied to phase-contrast and fluorescence images of cell migration, which visualize the cytoplasm, nuclei, or plasma/nuclear membranes. Many OF models have been developed [see (Delpiano et al, 2012) for some of these models applied to point signals in fluorescence images], the general idea is based on the hypothesis that the intensity/texture of local regions in time-varying images is approximately constant under motion, at least over short timescales This hypothesis leads to the so-called OF constraint equation, consisting of the spatial gradient and temporal firstorder partial derivative (speed) of the image intensity; see seminal surveys (Beauchemin and Barron, 1995; Fortun et al, 2015) for more information on mathematical formulation, computational methodology, and applications. The trajectories of the target tags are obtained by averaging velocity vectors within a local or segmented image region
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