Mechanical compression drives cancer cells toward invasive phenotype

Tse, Janet M.; Cheng, Gang; Tyrrell, James; Wilcox-Adelman, Sarah A.; Boucher, Yves; Jain, Rakesh K.; Munn, Lance L.

doi:10.1073/pnas.1118910109

Cited by 536 publications

(507 citation statements)

References 49 publications

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“…This notion is supported by breast cancer being more common with age as tissues stiffen, which aids disease progression 29 . Evidence of mechanics-based cancer growth has also been demonstrated by confining tumour growth to a small space, which promotes the emergence of leader cells 30 that increase the progression of metastasis. In these cases, the cells have random directionality under no load, but under compression, leader cells have a clear directionality that guides the movement of a group of cells.…”

Section: Bottom-up Assemblymentioning

confidence: 99%

The role of mechanics in biological and bio-inspired systems

et al. 2015

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Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering. N atural biological systems are constrained by a limited number of chemical building blocks, yet through practical material organization and mechanics 1 , fulfil the functional needs of diverse organisms by methods that often exceed what is currently achievable using man-made approaches 2 . Synthetic systems are often limited by trade-offs where improving one property comes at the expense of another, as observed when utilizing ceramics in place of metals where a higher elastic modulus is accompanied by lower fracture toughness. However, many natural systems and materials have evolved 3 solutions that result in a number of improved properties simultaneously (for example, high modulus with high fracture toughness), and often produce systems that fulfil multiple functions concurrently. For example, stomatopod dactyl clubs 4 tolerate exceptional amounts of damage through multiphasic material interfaces, and efficient blood-clotting mechanisms are achieved through platelet shape adaptability 5 . These intricate mechanics phenomena, relating material organization and adaptability, are implemented in a structurally minimalistic fashion that is difficult to emulate through artificial manufacturing approaches 6 . Such mechanical functions (that is, mechanofunctionality) of biological systems are not isolated cases-multiscale structural organization also contributes to the hardness of nacre 7 and toughness of toucan beaks 8 , while shape changing commonly drives behaviour in many sea creatures 9 and plants 10 . As such recurrent, mechanically based organizational features throughout biology are discovered and analysed, they provide insight for building exceptional mechanofunctionalities into synthetic, bio-inspired technologies.The survival of organisms is often heightened by structures and materials with favourable properties (for example, load-bearing capacity) or mechanofunctionalities that are passive

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Section: Bottom-up Assemblymentioning

confidence: 99%

The role of mechanics in biological and bio-inspired systems

et al. 2015

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“…Although the linear stability analysis fixes the thresholds and the wavelengths of the unstable wrinkling modes, the emerging three-dimensional pattern at the tumor surface will be driven by nonlinear effects. The postbuckling dynamics might promote tumor invasiveness through the formation of protrusions at the outer surface, which have been observed during the collective migration of invasive cells and vascular sprouting [29]. This work is in part supported by EU Grant No.…”

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confidence: 97%

Buckling Instability in Growing Tumor Spheroids

Ciarletta

2013

Phys. Rev. Lett.

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A growing tumor is subjected to intrinsic physical forces, arising from the cellular turnover in a spatially constrained environment. This work demonstrates that such residual solid stresses can provoke a buckling instability in heterogeneous tumor spheroids. The growth rate ratio between the outer shell of proliferative cells and the inner necrotic core is the control parameter of this instability. The buckled morphology is found to depend both on the elastic and the geometric properties of the tumor components, suggesting a key role of residual stresses for promoting tumor invasiveness.

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“…A quantitative description of the mechanical behaviour of groups of cells in biological tissues is critical for an understanding of many fundamental biological processes, including embryogenesis [1][2][3][4][5][6][7], wound healing [8,9], stem cell dynamics, regeneration [10,11] and tumourigenesis [12][13][14][15]. Previous work demonstrates that the macroscopic response of many tissues is viscoelastic [1], where the tissue behaves as an elastic solid over short timescales and a viscous fluid over long timescales.…”

Section: Introductionmentioning

confidence: 99%

Glassy dynamics in three-dimensional embryonic tissues

Schötz

Lanio

Talbot

et al. 2013

J. R. Soc. Interface.

133

137

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Many biological tissues are viscoelastic, behaving as elastic solids on short timescales and fluids on long timescales. This collective mechanical behaviour enables and helps to guide pattern formation and tissue layering. Here, we investigate the mechanical properties of three-dimensional tissue explants from zebrafish embryos by analysing individual cell tracks and macroscopic mechanical response. We find that the cell dynamics inside the tissue exhibit features of supercooled fluids, including subdiffusive trajectories and signatures of caging behaviour. We develop a minimal, three-parameter mechanical model for these dynamics, which we calibrate using only information about cell tracks. This model generates predictions about the macroscopic bulk response of the tissue (with no fit parameters) that are verified experimentally, providing a strong validation of the model. The best-fit model parameters indicate that although the tissue is fluid-like, it is close to a glass transition, suggesting that small changes to single-cell parameters could generate a significant change in the viscoelastic properties of the tissue. These results provide a robust framework for quantifying and modelling mechanically driven pattern formation in tissues.

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Mechanical compression drives cancer cells toward invasive phenotype

Cited by 536 publications

References 49 publications

The role of mechanics in biological and bio-inspired systems

The role of mechanics in biological and bio-inspired systems

Buckling Instability in Growing Tumor Spheroids

Glassy dynamics in three-dimensional embryonic tissues

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