期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：50
页码：15314-15319
DOI：10.1073/pnas.1510973112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCollective cell motion is very important in many biological processes such as wound healing, embryogenesis, or cancer progression. Nevertheless, it is not clear which parameters control the transition from freely moving single cells to collective jammed motion. In this article, we uncover complex dynamics as a cell monolayer ages, where cell motion is shown to gradually slow down with time, while the distance over which cell displacements are correlated first increases drastically and then decreases. This change of behavior is not controlled by cell density but rather by a maturation of the cell-cell and cell-substrate contacts. By comparing experiments, analytic model, and detailed particle-based simulations, we shed light on this biological amorphous solidification process. Although collective cell motion plays an important role, for example during wound healing, embryogenesis, or cancer progression, the fundamental rules governing this motion are still not well understood, in particular at high cell density. We study here the motion of human bronchial epithelial cells within a monolayer, over long times. We observe that, as the monolayer ages, the cells slow down monotonously, while the velocity correlation length first increases as the cells slow down but eventually decreases at the slowest motions. By comparing experiments, analytic model, and detailed particle-based simulations, we shed light on this biological amorphous solidification process, demonstrating that the observed dynamics can be explained as a consequence of the combined maturation and strengthening of cell-cell and cell-substrate adhesions. Surprisingly, the increase of cell surface density due to proliferation is only secondary in this process. This analysis is confirmed with two other cell types. The very general relations between the mean cell velocity and velocity correlation lengths, which apply for aggregates of self-propelled particles, as well as motile cells, can possibly be used to discriminate between various parameter changes in vivo, from noninvasive microscopy data.
