Biomechanical Microenvironment Regulates Fusogenicity of Breast Cancer Cells

Zhu, Pr; Tseng, Ning-Hsuan; Xie, Tianfa; Li, Ningwei; Fitts-Sprague, Isaac; Peyton, Shelly R.; Sun, Yubing

doi:10.1021/acsbiomaterials.8b00861

Cited by 13 publications

(14 citation statements)

References 68 publications

(169 reference statements)

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“…Cancer cell fusion is known to contribute to tumor development with fused cells having higher drug resistance. The metastatic MDA-MB-231 cell line formed multinucleated cells within confined patterns, but the typically stationary MCF-7 cell line did not (Zhu et al, 2019). Notably, multinucleated cells first formed on the edges of patterns in higher tension regions and later formed in the middle of patterned regions, revealing a potential strain-sensitive process for the multinucleation.…”

Section: Substrate Surface Patternsmentioning

confidence: 95%

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

Riehl

Kim

Bouzid

et al. 2021

Front. Bioeng. Biotechnol.

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Cancer can disrupt the microenvironments and mechanical homeostatic actions in multiple scales from large tissue modification to altered cellular signaling pathway in mechanotransduction. In this review, we highlight recent progresses in breast cancer cell mechanobiology focusing on cell-microenvironment interaction and mechanical loading regulation of cells. First, the effects of microenvironmental cues on breast cancer cell progression and metastasis will be reviewed with respect to substrate stiffness, chemical/topographic substrate patterning, and 2D vs. 3D cultures. Then, the role of mechanical loading situations such as tensile stretch, compression, and flow-induced shear will be discussed in relation to breast cancer cell mechanobiology and metastasis prevention. Ultimately, the substrate microenvironment and mechanical signal will work together to control cancer cell progression and metastasis. The discussions on breast cancer cell responsiveness to mechanical signals, from static substrate and dynamic loading, and the mechanotransduction pathways involved will facilitate interdisciplinary knowledge transfer, enabling further insights into prognostic markers, mechanically mediated metastasis pathways for therapeutic targets, and model systems required to advance cancer mechanobiology.

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Section: Substrate Surface Patternsmentioning

confidence: 95%

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

Riehl

Kim

Bouzid

et al. 2021

Front. Bioeng. Biotechnol.

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“…Soft lithography was used to generate patterned polydimethylsiloxane (PDMS) stamps from negative SU8 molds that were fabricated using photolithography. These PDMS stamps were used to generate patterned cell colonies using microcontact printing, as described previously ( Zhu et al, 2019 ). Briefly, to generate patterned cell colonies on flat PDMS surfaces, round glass coverslips (diameter = 25 mm, Fisher Scientific) were spin-coated (Spin Coater; Laurell Technologies) with a thin layer of PDMS prepolymer comprising of PDMS base monomer and curing agent (10:1 w / w ; Sylgard 184, Dow-Corning).…”

Section: Methodsmentioning

confidence: 99%

Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers

Xie

Pierre

Olaranont

et al. 2021

eLife

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A monolayer of highly motile cells can establish long-range orientational order, which can be explained by hydrodynamic theory of active gels and fluids. However, it is less clear how cell shape changes and rearrangement are governed when the monolayer is in mechanical equilibrium states when cell motility diminishes. In this work, we report that rat embryonic fibroblasts (REF), when confined in circular mesoscale patterns on rigid substrates, can transition from the spindle shapes to more compact morphologies. Cells align radially only at the pattern boundary when they are in the mechanical equilibrium. This radial alignment disappears when cell contractility or cell-cell adhesion is reduced. Unlike monolayers of spindle-like cells such as NIH-3T3 fibroblasts with minimal intercellular interactions or epithelial cells like Madin-Darby canine kidney (MDCK) with strong cortical actin network, confined REF monolayers present an actin gradient with isotropic meshwork, suggesting the existence of a stiffness gradient. In addition, the REF cells tend to condense on soft substrates, a collective cell behavior we refer to as the 'condensation tendency'. This condensation tendency, together with geometrical confinement, induces tensile prestretch (i.e., an isotropic stretch that causes tissue to contract when released) to the confined monolayer. By developing a Voronoi-cell model, we demonstrate that the combined global tissue prestretch and cell stiffness differential between the inner and boundary cells can sufficiently define the cell radial alignment at the pattern boundary.

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“…The few cells trapped between the micropillars were excluded. If only preferential attachment to the top of the micropillars is required, it can be achieved by only performing coating on the top of the micropillars using contact microprinting of protein on the top of the micropillars [41], and defunctionalization of the sides of the micropillars using solvents such as Pluronic F-127 [42]. In Fig.…”

Section: Discussionmentioning

confidence: 99%

Guided cell migration on a graded micropillar substrate

Krishnamoorthy

Zhang

2020

Bio-des. Manuf.

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Cell migration is facilitated by the interaction of living cells and their local microenvironment. The local topography is one of the key factors regulating cell migration. Interaction between the surface topography and the cell behaviors is critical to understanding tissue development and regeneration. In this study, a dynamic mask photolithography technique has been utilized to fabricate a surface with graded micropillars. It has been demonstrated that the cells have been successfully guided to migrate from the sparse zone to the dense zone. The cell polarization angle has been characterized in both sparse zone and the dense zone. Compared to the dense zone, the cells in the sparse zone are more aligned along the direction of the micropillar spacing gradient, which enables the guided cell migration. Moreover, the effects of the micropillar spacing gradient, micropillar diameter, and micropillar height have been investigated in terms of the cell migration speed and cell spreading area. Finally, two issues significantly affecting the cell migration have been discussed: trapped cells between the micropillars and cell clusters.

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Biomechanical Microenvironment Regulates Fusogenicity of Breast Cancer Cells

Cited by 13 publications

References 68 publications

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers

Guided cell migration on a graded micropillar substrate

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