Collective motion of mammalian cell cohorts in 3D

Abstract

Collective cell migration is ubiquitous in biology, from development to cancer; it occurs in complex systems comprised of heterogeneous cell types, signals and matrices, and requires large scale regulation in space and time. Understanding how cells achieve organized collective motility is crucial to addressing cellular and tissue function and disease progression. While current two-dimensional model systems recapitulate the dynamic properties of collective cell migration, quantitative three-dimensional equivalent model systems have proved elusive. To establish such a model system, we study cell collectives by tracking individuals within cell cohorts embedded in three dimensional collagen scaffolding. We develop a custom algorithm to quantify the temporal and spatial heterogeneity of motion in cell cohorts during motility events. In the absence of external driving agents, we show that these cohorts rotate in short bursts, <2 hours, and translate for up to 6 hours. We observe, track, and analyze three dimensional motion of cell cohorts composed of 3–31 cells, and pave a path toward understanding cell collectives in 3D as a complex emergent system.

Impact of the physical microenvironment on tumor progression and metastasis

“…How collectively migrating cells depend on leader cells, or can self-organize, is itself an ongoing research effort [21]. This research also has potential clinical applications.…”

Semblance of heterogeneity in collective cell migration

“…In this paper, we have implemented both free (cells are unconfined) and no-flux (reflective) boundary conditions. A similar 3D model has also been developed by Sharma et al (2015), with small but important differences in the model implementation. Crucially, we have kept the original idea by Grégoire et al (2003) to restrict interactions to nearest Voronoi neighbors.…”

“…Heterogeneity of cell migration is of great interest to cancer research, for example to identify whether a subpopulation of cells in a tumor is more invasive, and how this invasive behaviour can be modulated by drugs or microenvironmental properties. Recent studies of mammalian cell cohorts in 3D environments have used delay correlation analysis to quantify heterogeneity (Sharma et al, 2015). The authors found a range of delay distributions of different cell clusters, indicating potential evidence for heterogeneity of movement between different cell clusters (although making no direct claim as to any underlying heterogeneity of cell states themselves).…”

“…Comparison with experimental data Sharma et al (2015) conduct analysis of mammalian cell cohorts in 3D. In particular, they report broad peak-delay distributions of clusters of N c1 = 10 and N c2 = 19 cells.…”

Modeling, signaling and cytoskeleton dynamics: integrated modeling‐experimental frameworks in cell migration

“…Utilization of these tools has made it possible to track not only cellular motion velocity but also directional migration persistence, mean‐squared displacement (MSD), the velocity correlation, the cell‐pair separation distance, and so on. Nonetheless, more quantified variables are needed to quantify and distinguish different patterns of migration modes in both single‐cell and collective cell migration, such as transition between amoeboid and mesenchymal migration, cellular leadership in collective behavior . Additionally, not all tools are applicable in native like three‐dimensional environments.…”