Mechanical Interaction of Metastatic Cancer Cells with a Soft Gel

Kristal-Muscal, Revital; Dvir, Liron; Schvartzer, Maayan; Weihs, Daphne

doi:10.1016/j.piutam.2014.12.023

Cited by 16 publications

(10 citation statements)

References 60 publications

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“…The main roles of the CSK are to: (i) spatially organize the cell contents, by maintaining local and global (cell-wide) structure and facilitating intracellular transport; (ii) connect the cell to its external environment, e.g. to neighboring cells or the extracellular matrix (ECM), and mechanically stabilize the PM, and (iii) generate coordinated forces that enable shape changes and movements [4,5] . The Weihs group has previously shown that disruption of specific elements of the CSK reduces cell adhesion and forces that (cancer) cells apply to a soft gel [6] , and also affects cell morphology, overall CSK organization and dynamics of intracellular transport [7,8] .…”

Section: Cytoskeletal Mechanics and Dynamicsmentioning

confidence: 99%

“…Single cells and monolayers have been shown to directly interact with the environment, changing their morphology, applying force and deforming the substrate and neighboring cells [34,35] . Specifically, the Weihs lab have shown that single cancer cells may locally deform soft elastic gels, by modifying their internal structures to facilitate force application [5,36,37] , an ability which correlates directly with their tendency to invade adjacent tissue. Mechanical interactions of cells with their substrates have also been shown to affect differentiation, alignment, and migration capabilities [38][39][40] .…”

Section: Applying and Estimating Dynamic Deformations And Responses Omentioning

confidence: 99%

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Cytoskeleton and plasma-membrane damage resulting from exposure to sustained deformations: A review of the mechanobiology of chronic wounds

Gefen

Weihs

2016

Medical Engineering & Physics

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Section: Cytoskeletal Mechanics and Dynamicsmentioning

confidence: 99%

Section: Applying and Estimating Dynamic Deformations And Responses Omentioning

confidence: 99%

Cytoskeleton and plasma-membrane damage resulting from exposure to sustained deformations: A review of the mechanobiology of chronic wounds

Gefen

Weihs

2016

Medical Engineering & Physics

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“…For instance, observations on how cells migrate and behave within these artificial networks allowed determining how nuclear size, cell deformability, and cell adhesion on substrates may affect tissue invasion efficiency, or uncovering enhanced directional migration of cancer cells in anisotropic porous scaffolds . In vitro hydrogel‐based systems to study cell migration have been widely used for investigating cell mechanics, revealing that increased ECM rigidity can improve cell migration and protrusion formation and, more in general, invasive cells' behavior can differ depending on environmental rigidity …”

Section: Introductionmentioning

confidence: 99%

“…In this context, two‐photon lithography (2PL) has shown its potential for creating well‐controlled 3D microenvironments in terms of structural precision, including complex architectures to investigate cell mechanics. Examples for that are the elastic scaffolds proposed by Klein et al to quantify forces applied by cardiomyocytes during contraction, and by Greiner et al to study cell migration in the presence of chemoattractant gradients in microporous scaffolds. 2PL microstructures were also selectively functionalized by Richter et al with distinct ECM proteins to achieve targeted and cell‐type‐specific adhesion.…”

Section: Introductionmentioning

confidence: 99%

Microenvironmental Stiffness of 3D Polymeric Structures to Study Invasive Rates of Cancer Cells

Lemma

Spagnolo

Rizzi

et al. 2017

Adv Healthcare Materials

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Cells are highly dynamic elements, continuously interacting with the extracellular environment. Mechanical forces sensed and applied by cells are responsible for cellular adhesion, motility, and deformation, and are heavily involved in determining cancer spreading and metastasis formation. Cell/extracellular matrix interactions are commonly analyzed with the use of hydrogels and 3D microfabricated scaffolds. However, currently available techniques have a limited control over the stiffness of microscaffolds and do not allow for separating environmental properties from biological processes in driving cell mechanical behavior, including nuclear deformability and cell invasiveness. Herein, a new approach is presented to study tumor cell invasiveness by exploiting an innovative class of polymeric scaffolds based on two-photon lithography to control the stiffness of deterministic microenvironments in 3D. This is obtained by fine-tuning of the laser power during the lithography, thus locally modifying both structural and mechanical properties in the same fabrication process. Cage-like structures and cylindric stent-like microscaffolds are fabricated with different Young's modulus and stiffness gradients, allowing obtaining new insights on the mechanical interplay between tumor cells and the surrounding environments. In particular, cell invasion is mostly driven by softer architectures, and the introduction of 3D stiffness "weak spots" is shown to boost the rate at which cancer cells invade the scaffolds. The possibility to modulate structural compliance also allowed estimating the force distribution exerted by a single cell on the scaffold, revealing that both pushing and pulling forces are involved in the cell-structure interaction. Overall, exploiting this method to obtain a wide range of 3D architectures with locally engineered stiffness can pave the way for unique applications to study tumor cell dynamics.

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“…This is motivated by the experimentally observed Poisson ratio of 0.48 (Massalha and Weihs 2017 ; Kristal-Muscal et al. 2015 ). The above relation is able to handle the non-uniformity of the substrate stiffness.…”

Section: Mathematical Modelmentioning

confidence: 93%

A model for cell migration in non-isotropic fibrin networks with an application to pancreatic tumor islets

Chen

Weihs

Vermolen

2017

Biomech Model Mechanobiol

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Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk. The stochastic differential equations are solved by the use of the classical Euler–Maruyama method. In this paper, the influence of anisotropic stromal extracellular matrix in pancreatic tumor islets on T-lymphocytes migration in different immune systems is investigated. As a result, tumor peripheral stromal extracellular matrix impedes the immune response of T-lymphocytes through changing direction of their migration.Electronic supplementary materialThe online version of this article (doi:10.1007/s10237-017-0966-7) contains supplementary material, which is available to authorized users.

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Mechanical Interaction of Metastatic Cancer Cells with a Soft Gel

Cited by 16 publications

References 60 publications

Cytoskeleton and plasma-membrane damage resulting from exposure to sustained deformations: A review of the mechanobiology of chronic wounds

Cytoskeleton and plasma-membrane damage resulting from exposure to sustained deformations: A review of the mechanobiology of chronic wounds

Microenvironmental Stiffness of 3D Polymeric Structures to Study Invasive Rates of Cancer Cells

A model for cell migration in non-isotropic fibrin networks with an application to pancreatic tumor islets

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