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乳腺癌细胞趋化运动过程中的精度和持久性的物理约束。

Physical constraints on accuracy and persistence during breast cancer cell chemotaxis.

机构信息

Department of Physics and Astronomy, Purdue University, West Lafayette, Indiana, United States of America.

School of Mechanical Engineering, Purdue University, West Lafayette Indiana, United States of America.

出版信息

PLoS Comput Biol. 2019 Apr 10;15(4):e1006961. doi: 10.1371/journal.pcbi.1006961. eCollection 2019 Apr.

Abstract

Directed cell motion in response to an external chemical gradient occurs in many biological phenomena such as wound healing, angiogenesis, and cancer metastasis. Chemotaxis is often characterized by the accuracy, persistence, and speed of cell motion, but whether any of these quantities is physically constrained by the others is poorly understood. Using a combination of theory, simulations, and 3D chemotaxis assays on single metastatic breast cancer cells, we investigate the links among these different aspects of chemotactic performance. In particular, we observe in both experiments and simulations that the chemotactic accuracy, but not the persistence or speed, increases with the gradient strength. We use a random walk model to explain this result and to propose that cells' chemotactic accuracy and persistence are mutually constrained. Our results suggest that key aspects of chemotactic performance are inherently limited regardless of how favorable the environmental conditions are.

摘要

细胞在外部化学梯度的作用下定向运动存在于许多生物学现象中,如伤口愈合、血管生成和癌症转移。趋化性的特征通常包括细胞运动的准确性、持久性和速度,但这些量是否受到其他量的物理限制还知之甚少。我们使用理论、模拟和对单个转移性乳腺癌细胞的 3D 趋化性测定的组合,研究了这些趋化性性能不同方面之间的联系。特别是,我们在实验和模拟中都观察到,趋化性的准确性而不是持久性或速度随着梯度强度的增加而增加。我们使用随机游动模型来解释这一结果,并提出细胞的趋化性准确性和持久性是相互制约的。我们的结果表明,无论环境条件多么有利,趋化性性能的关键方面都是固有受限的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392b/6476516/dff1f5f206ea/pcbi.1006961.g001.jpg

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