A frequency-based hypothesis for mechanically targeting and selectively attacking cancer cells

Fraldi, Massimiliano; Cugno, Andrea; Deseri, Luca; Dayal, Kaushik; Pugno, Nicola

doi:10.1098/rsif.2015.0656

Cited by 55 publications

(60 citation statements)

References 59 publications

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“…deformability) than RGP and VGP cells, whereas the fluidity of VGP cells was similar (8.3% higher) to that of RGP cells. These results agree with many studies (Fraldi et al 2015, Gal and Weihs 2012, Guck et al 2005, which indicate that more motile cells in an advanced disease stage are more deformable than less motile cancer cells at earlier disease stages.…”

Section: Discussionsupporting

confidence: 92%

Cytoskeletal Tubulin Competes with Actin to Increase Deformability of Metastatic Melanoma Cells

Higgins

Peres

Abdalrahman

et al. 2020

Preprint

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The formation of membrane protrusions during migration is reliant upon the cells' cytoskeletal structure and stiffness. It has been reported that actin disruption blocks protrusions and decreases cell stiffness whereas microtubule disruption blocks protrusion but increases stiffness in several cell types. In melanoma, cell migration is of concern as this cancer spreads unusually rapidly during early tumour development. The aim of this study was to characterise motility, structural properties and stiffness of human melanoma cells at radial growth phase (RGP), vertical growth phase (VGP), and metastatic stage (MET) in two-dimensional in vitro environments. Wound assays, western blotting and mitochondrial particle tracking were used to assess cell migration, cytoskeletal content and intracellular fluidity. Our results indicate that cell motility increase with increasing disease stage. Despite their different motility, RGP and VGP cells exhibit similar fluidity, actin and tubulin levels. MET cells, however, display increased fluidity which was associated with increased actin and tubulin content. Our findings demonstrate an interplay between actin and microtubule activity and their role in increasing motility of cells while minimizing cell stiffness at advanced disease stage. In earlier disease stages, cell stiffness may however not serve as an indicator of migratory capabilities.

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Section: Discussionsupporting

confidence: 92%

Cytoskeletal Tubulin Competes with Actin to Increase Deformability of Metastatic Melanoma Cells

Higgins

Peres

Abdalrahman

et al. 2020

Preprint

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“…However, the cell initial (tangent) stiffness is significantly different in the two cases considered ( Figure 10): for the neo-Hookean case, it monotonically increases as the pre-stretch in the cables increases, as actually found in some theoretical predictions [62] and experimental results [63], while -for the Hencky model-the initial stiffness shows a counterintuitive decreasing path from a selected threshold similar to that found by Coughlin and Stamenovic in their "round" tensegrity model comprising rigid struts [23,27], that however seems to have not been experimentally observed so far. Finally, from the quantitative point of view, we noticed that the values of the overall cell stiffness obtained by modeling the cytoskeleton as a soft-strut tensegrity, gave values of the order of magnitude of about 10 2 − 10 3 P a, spanning over a reasonable wide range of prestress, in line with the most commonly ascertained values of stiffness measured in the literature through several experimental techniques, for different healthy and cancer cell lines [64,3]. By way of example, it can be useful to compare the initial (tangent) stiffness evaluated for the proposed soft tensegrity model with that provided by a classical rigid-strut one.…”

Section: Crushing and Stretching Of Cells: Contraction And Elongationsupporting

confidence: 84%

Buckling soft tensegrities: Fickle elasticity and configurational switching in living cells

Fraldi

Palumbo

Carotenuto³

et al. 2019

Journal of the Mechanics and Physics of Solids

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Tensegrity structures are special architectures made by floating compressed struts kept together by a continuous system of tensioned cables. Their existence in a mechanically stable form is decided by the possibility of finding geometrical configurations such that pre-stressed tendons and bars can ensure self-equilibrium of the forces transmitted through the elastic network, the overall stiffness of which finally depends on both the rigidity of the compressed elements and the cables' pre-stress. The multiplicity of shapes that tensegrity structures can assume and their intrinsic capability to be deployable and assembled, so storing (and releasing) elastic energy, have motivated their success as paradigm -pioneeringly proposed three decades ago by the intuition of Donald E. Ingber-to explain some underlying mechanisms regulating dynamics of living cells. The interlaced structure of the cell cytoskeleton, constituted by actin microfilaments, intermediate filaments and microtubules which continuously change their spatial organization and pre-stresses through polymerization/depolymerization processes, seems in fact to steer migration, adhesion and arXiv:1904.04610v1 [physics.bio-ph] 9 Apr 2019 cell division by obeying the tensegrity construct. Even though rough calculations lead to estimate discrepancies of less than one order of magnitude when comparing axial stiffness of actin filaments (cables) and microtubules (struts) and recent works have shown bent microtubules among stretched filaments, no one has yet tried to remove the standard hypothesis of rigid struts in tensegrity structures when used to idealize the cell cytoskeleton mechanical response. With reference to the 30-element tensegrity cell paradigm, we thus introduce both compressibility and bendability of the struts and accordingly rewrite the theory to simultaneously take into account geometrical non-linearity (i.e. large deformations) and hyper-elasticity of both tendons and bars, so abandoning the classical linear stress-strain constitutive assumptions. By relaxing the hypothesis of rigidity of the struts, we demonstrate that some quantitative confirmations and many related extreme and somehow counterintuitive mechanical behaviors actually exploited by cells for storing/releasing energy, resisting to applied loads and deforming by modulating their overall elasticity and shape through pre-stress changes and instability-guided configurational switching, can be all theoretically found. It is felt that the proposed new soft-strut tensegrity model could pave the way for a wider use of engineering models in cell mechanobiology and in designing bio-inspired materials and soft robots.

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“…The effect of an imperfect capsule alignment on the inlet channel centerline is also inves- Elastic capsules and soft beads are good models for biological cells [4,5]. Since many pathologies can significantly modify cell deformability, e.g., softening cells from three to ten times [5], our numerical results give a proof of concept on the possibility of separating diseased cells from healthy ones, thus leading to illness diagnosis.…”

Section: Discussionmentioning

confidence: 72%

“…Since many pathologies can significantly modify cell deformability, e.g., softening cells from three to ten times [5], our numerical results give a proof of concept on the possibility of separating diseased cells from healthy ones, thus leading to illness diagnosis.…”

Section: Discussionmentioning

confidence: 90%

“…In this regard, another interesting target for selective separation are circulating tumor cells (CTCs), which are responsible for blood-borne metastasis and most cancer-related deaths [22]. It is known from the literature that diseased cells can soften 3 to 10 times with respect to healthy ones (see [5] and the references therein), thus the difference in cell stiffness might be used to discriminate neoplastic transformations in cell samples, leading to possible applications in the diagnosis and treatment of cancer diseases.…”

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confidence: 99%

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Numerical design of a T-shaped microfluidic device for deformability-based separation of elastic capsules and soft beads

2017

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Document VersionAccepted manuscript including changes made at the peer-review stage Please check the document version of this publication:• A submitted manuscript is the author's version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website.• The final author version and the galley proof are versions of the publication after peer review.• The final published version features the final layout of the paper including the volume, issue and page numbers. (2017). Numerical design of a T-shaped microfluidic device for deformability-based separation of elastic capsules and soft beads. Physical Review E, 96(5), [053103]. DOI: 10.1103/PhysRevE.96.053103 Link to publication Citation for published version (APA): General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. We propose a square cross section microfluidic channel with an orthogonal side branch (asymmetric T-shaped bifurcation) for the separation of elastic capsules and soft beads suspended in a Newtonian liquid on the basis of their mechanical properties.The design is performed through 3D direct numerical simulations.When suspended objects start near the inflow channel centerline and the carrier fluid is equally partitioned between the two outflow branches, particle separation can be achieved based on their deformability, with the stiffer ones going 'straight' and the softer ones being deviated to the 'side' branch. The effects of the geometrical and physical parameters of the system on the phenomenon are investigated.Since cell deformability can be significantly modified by pathology, we give a proof of concept on the possibility of separating diseased cells from healthy ones, thus leading to illness diagnosis.

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A frequency-based hypothesis for mechanically targeting and selectively attacking cancer cells

Cited by 55 publications

References 59 publications

Cytoskeletal Tubulin Competes with Actin to Increase Deformability of Metastatic Melanoma Cells

Cytoskeletal Tubulin Competes with Actin to Increase Deformability of Metastatic Melanoma Cells

Buckling soft tensegrities: Fickle elasticity and configurational switching in living cells

Numerical design of a T-shaped microfluidic device for deformability-based separation of elastic capsules and soft beads

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