Author:
Kravchenko-Balasha Nataly,Shin Young Shik,Sutherland Alex,Levine R. D.,Heath James R.
Abstract
Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell–cell signaling can depend on cell–cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell–cell signaling that induces a directed cell–cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell–cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell–cell distances. We show that glioblastoma cell–cell movement can be described as Brownian motion biased by cell–cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.
Publisher
Proceedings of the National Academy of Sciences
Reference28 articles.
1. Lodish H (2000) Molecular Cell Biology (W. H. Freeman, New York), 4th Ed
2. Physical Limits on Cellular Sensing of Spatial Gradients
3. The physics of eukaryotic chemotaxis;Levine;Phys Today,2013
4. Robustness in bacterial chemotaxis
5. Alberts B (2002) Cell Motility in Cancer Invasion and Metastasis Molecular Biology of the Cell (Garland Science, New York)
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