Geometric Dependence of 3D Collective Cancer Invasion

Kim, Jihan; Zheng, Yu; Alobaidi, Amani A.; Nan, Hanqing; Tian, Jianxiang; Jiao, Yang; Sun, Bo

doi:10.1016/j.bpj.2020.01.008

Cited by 31 publications

(29 citation statements)

References 33 publications

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“…Contact guidance has also been observed for cells in 3D ECMs. For instance, we and other groups have shown that ECM fiber alignment, either engineered by external stress or induced by cell-generated forces, is able to bias the polarization and migration of cancer cells in vitro (19,20). Clini-cally, contact guidance regulates metastasis of cancer cells during dissemination and thus correlates with the prognosis of cancer patients (21).…”

mentioning

confidence: 99%

The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance

Kim

Cao

Eddy

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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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.

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mentioning

confidence: 99%

The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance

Kim

Cao

Eddy

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…In the present model, the cell–ECM boundary was simplified to a gradient of the ECM field to quantify the resistance force. However, at the cell level, other mechanical remodelling events also occur in the ECM, for example, fibre re-alignment owing to cell traction force and the orientation of surrounding cells 61 – 63 , and these events also have an effect on cellular migration 64 , although they likely occur prior to the degradation of the resistance force. Interface instability, particularly where boundary conditions change steeply between the cell–ECM and ECM-tunnel region, is also likely involved in the current system, and is thought to contribute morphogen diffusion to cause chemotaxis.…”

Section: Discussionmentioning

confidence: 99%

Weakening of resistance force by cell–ECM interactions regulate cell migration directionality and pattern formation

et al. 2021

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Collective migration of epithelial cells is a fundamental process in multicellular pattern formation. As they expand their territory, cells are exposed to various physical forces generated by cell–cell interactions and the surrounding microenvironment. While the physical stress applied by neighbouring cells has been well studied, little is known about how the niches that surround cells are spatio-temporally remodelled to regulate collective cell migration and pattern formation. Here, we analysed how the spatio-temporally remodelled extracellular matrix (ECM) alters the resistance force exerted on cells so that the cells can expand their territory. Multiple microfabrication techniques, optical tweezers, as well as mathematical models were employed to prove the simultaneous construction and breakage of ECM during cellular movement, and to show that this modification of the surrounding environment can guide cellular movement. Furthermore, by artificially remodelling the microenvironment, we showed that the directionality of collective cell migration, as well as the three-dimensional branch pattern formation of lung epithelial cells, can be controlled. Our results thus confirm that active remodelling of cellular microenvironment modulates the physical forces exerted on cells by the ECM, which contributes to the directionality of collective cell migration and consequently, pattern formation.

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“…The increase in peripheral tension compresses the surrounding matrix and facilitates normal duct formation and outward collective cell migration. 158,160 In pathogenic conditions, reducing the peripheral contractility of cells in the tumor decreases their invasive potential in both breast cancer 166 and fibrosarcomas. 165 These contrasting observations suggest an optimal tensile balance at the microtissue periphery, which is essential for maintaining homeostatic architecture.…”

Section: Measuring Forces At the Tissue Length Scalementioning

confidence: 99%

“… 225 The unjamming process seems to play a key role in breast cancer progression, where the decrease in compressive stresses enhances collective migration in more invasive cancers. 166 …”

Section: Emerging Views Of Tensegrity In Biologymentioning

confidence: 99%

Revisiting tissue tensegrity: Biomaterial-based approaches to measure forces across length scales

et al. 2021

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Cell-generated forces play a foundational role in tissue dynamics and homeostasis and are critically important in several biological processes, including cell migration, wound healing, morphogenesis, and cancer metastasis. Quantifying such forces in vivo is technically challenging and requires novel strategies that capture mechanical information across molecular, cellular, and tissue length scales, while allowing these studies to be performed in physiologically realistic biological models. Advanced biomaterials can be designed to non-destructively measure these stresses in vitro , and here, we review mechanical characterizations and force-sensing biomaterial-based technologies to provide insight into the mechanical nature of tissue processes. We specifically and uniquely focus on the use of these techniques to identify characteristics of cell and tissue “tensegrity:” the hierarchical and modular interplay between tension and compression that provide biological tissues with remarkable mechanical properties and behaviors. Based on these observed patterns, we highlight and discuss the emerging role of tensegrity at multiple length scales in tissue dynamics from homeostasis, to morphogenesis, to pathological dysfunction.

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Geometric Dependence of 3D Collective Cancer Invasion

Cited by 31 publications

References 33 publications

The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance

The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance

Weakening of resistance force by cell–ECM interactions regulate cell migration directionality and pattern formation

Revisiting tissue tensegrity: Biomaterial-based approaches to measure forces across length scales

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