气候变化领域集成服务门户(CCPortal): The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance

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DOI	10.1073/pnas.2024780118
	The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance
	Kim J.; Cao Y.; Eddy C.; Deng Y.; Levine H.; Rappel W.-J.; Sun B.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Contact guidance is a major physical cue that modulates cancer cell morphology and motility, and is directly linked to the prognosis of cancer patients. Under physiological conditions, particularly in the three-dimensional (3D) extracellular matrix (ECM), the disordered assembly of fibers presents a complex directional bias to the cells. It is unclear how cancer cells respond to these noncoherent contact guidance cues. Here we combine quantitative experiments, theoretical analysis, and computational modeling to study the morphological and migrational responses of breast cancer cells to 3D collagen ECM with varying degrees of fiber alignment. We quantify the strength of contact guidance using directional coherence of ECM fibers, and find that stronger contact guidance causes cells to polarize more strongly along the principal direction of the fibers. Interestingly, sensitivity to contact guidance is positively correlated with cell aspect ratio, with elongated cells responding more strongly to ECM alignment than rounded cells. Both experiments and simulations show that cell–ECM adhesions and actomyosin contractility modulate cell responses to contact guidance by inducing a population shift between rounded and elongated cells. We also find that cells rapidly change their morphology when navigating the ECM, and that ECM fiber coherence modulates cell transition rates between different morphological phenotypes. Taken together, we find that subcellular processes that integrate conflicting mechanical cues determine cell morphology, which predicts the polarization and migration dynamics of cancer cells in 3D ECM. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cell motility; Contact guidance; Extracellular matrix; Phenotypic transition
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180414
作者单位	Department of Physics, Oregon State University, Corvallis, OR 97331, United States; Department of Physics, University of California San Diego, San diego, CA 92093, United States; Center for Theoretical Biological Physics, Northeastern University, Boston, MA 02115, United States; Department of Physics, Northeastern University, Boston, MA 02115, United States; Department of Bioengineering, Northeastern University, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Kim J.,Cao Y.,Eddy C.,et al. The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance[J],2021,118(10).
APA	Kim J..,Cao Y..,Eddy C..,Deng Y..,Levine H..,...&Sun B..(2021).The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Kim J.,et al."The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).