Cell Division Induces and Switches Coherent Angular Motion within Bounded Cellular Collectives

Abstract

Collective cell migration underlies many biological processes, including embryonic development, wound healing, and cancer progression. In the embryo, cells have been observed to move collectively in vortices using a mode of collective migration known as coherent angular motion (CAM). To determine how CAM arises within a population and changes over time, here, we study the motion of mammary epithelial cells within engineered monolayers, in which the cells move collectively about a central axis in the tissue. Using quantitative image analysis, we find that CAM is significantly reduced when mitosis is suppressed. Particle-based simulations recreate the observed trends, suggesting that cell divisions drive the robust emergence of CAM and facilitate switches in the direction of collective rotation. Our simulations predict that the location of a dividing cell, rather than the orientation of the division axis, facilitates the onset of this motion. These predictions agree with experimental observations, thereby providing, to our knowledge, new insight into how cell divisions influence CAM within a tissue. Overall, these findings highlight the dynamic nature of CAM and suggest that regulating cell division is crucial for tuning emergent collective migratory behaviors, such as vortical motions observed in vivo.

Coherent motion of dense active matter

“…The circulations were destroyed by knocking out cell-cell junctions, emphasising the importance of collective interactions in driving the coherent flow patterns. Cell division has also been implicated in driving rotation of cell clusters [29,30]. The cells also performed regular breathing oscillations in the radial direction.…”

Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma

“…Moreover, to further confirm that the features observed were not an artifact of tissue slicing (i.e., the extruded cells were indeed discrete entities and not part of a larger ductal network connected in other planes), we reconstructed the 3D volume around entire ductal structures using multiphoton imaging of live early disease tumor samples, and we again confirmed the existence of single carcinoma cells in the stroma ( Figure 3B and Supplemental Video 1 ). Interestingly, long-term imaging of ductal structures also revealed dynamic rearrangement and rotational movement of the epithelium, a phenomenon known as coherent angular motion ( Supplemental Video 2 ), which has been previously observed in vitro in mammary acini ( 39 , 40 ) and is thought to be sustained, in part, by cell division ( 40 ). Our observation of this phenomenon in live premalignant and malignant tissue further demonstrates the dynamic nature of epithelial cells in organized ductal structures.…”

Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma

“…3b, Movie 1). Interestingly, long-term imaging of ductal structures also revealed dynamic rearrangement and rotational movement of the epithelium, a phenomenon known as coherent angular motion (Movie 2), which has been previously observed in vitro in mammary acini ( 42, 43 ), and is thought to be sustained, in part, by cell division ( 43 ). Our observation of this phenomenon in live pre-malignant and malignant tissue further demonstrates the dynamic nature of epithelial cells in organized ductal structures.…”