Viscoelastic properties of microgel thin films control fibroblast modes of migration and pro-fibrotic responses

Chester, Daniel; Kathard, Rahul; Nortey, Jeremy; Nellenbach, Kimberly; Brown, Ashley

doi:10.1016/j.biomaterials.2018.09.012

Cited by 32 publications

(54 citation statements)

References 55 publications

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“…Brown's group reported that viscoelastic feature of the microgel thin films efficiently controlled modes of migration in fibroblasts ( Figure A). [ 197 ] On thin films with the highest loss tangent value (e.g., 1% BIS films), round or ellipsoid fibroblasts with poor stress fiber loosely attached to the substrates. These cells demonstrated slow rates of migration and decreased spreading area, suggesting that amoeboid cell migration occurred; On thin films with the lowest loss tangent value (e.g., 7% BIS films), elongated fibroblasts with robust stress fiber formed strong substrate adhesion, indicating dominating mesenchymal migration; On films with intermediate loss tangent values (e.g., 2% and 4% BIS films), a transition between amoeboid and mesenchymal migration happened.…”

Section: Viscoelastic Cell Microenvironment Affects Cell Behavior and Fatementioning

confidence: 99%

Section: Viscoelastic Cell Microenvironment Affects Cell Behavior and Fatementioning

confidence: 99%

“…Furthermore, Brown's group studied relaxation rate‐dependent cell phenotypic change of dermal fibroblasts on viscoelastic microgel thin films. [ 197 ] Dermal fibroblasts on films with lower loss tangent values showed more stress fiber formation and higher expression of connective tissue growth factor (CTGF, fibrosis associated growth factors) than that of cells on higher loss tangent films, which indicated that slow relaxing substrates promoted phenotypic switch from fibroblasts to myofibroblasts. In addition, epithelial‐mesenchymal transition (EMT) is an important phenomenon of cell phenotypic switch that induces cancer metastasis.…”

Section: Viscoelastic Cell Microenvironment Affects Cell Behavior and Fatementioning

confidence: 99%

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Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Han

Yang

et al. 2021

Adv Funct Materials

113

121

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The native extracellular matrix (ECM) generally exhibits dynamic mechanical properties and displays time‐dependent responses to deformation or mechanical loading, in terms of viscoelastic behaviors (e.g., stress relaxation and creep). Viscoelasticity of the ECM plays a critical role in development, homeostasis, and tissue regeneration, and its implication in disease progression has also been recognized recently. Hydrogels with tunable viscoelastic properties hold a great promise to recapitulate such time‐dependent mechanics found in native ECM, which have been recently used to regulate cell behavior and guide cell fate. Here the importance of tissue viscoelasticity is first highlighted, the molecular mechanisms of hydrogel viscoelasticity are summarized, and characterization techniques used at the macroscale and microscale are reviewed. Then, recent advances in developing novel hydrogels with tunable viscoelasticity through varying crosslinking strategies, engineering of viscoelastic cell microenvironment and its substantial effects on cell behavior and fate are described, and the underlying mechanobiology mechanisms are subsequently discussed. Finally, the ongoing challenges and future perspectives on the design and modulation of viscoelastic hydrogels and the mechanobiology mechanisms on cellular responses to viscoelastic cell microenvironment are proposed.

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Section: Viscoelastic Cell Microenvironment Affects Cell Behavior and Fatementioning

confidence: 99%

Section: Viscoelastic Cell Microenvironment Affects Cell Behavior and Fatementioning

confidence: 99%

Section: Viscoelastic Cell Microenvironment Affects Cell Behavior and Fatementioning

confidence: 99%

See 1 more Smart Citation

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Han

Yang

et al. 2021

Adv Funct Materials

113

121

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“…Other hydrogel systems with controllable viscoelastic properties are based on microgel films. These are produced by deposition, usually layer‐by‐layer, of discrete hydrogel particles (microgels) with sizes ranging from the nanometers to micrometers . An earlier report showed that their viscoelastic behavior, beside granting them the ability to self‐heal after stretching in the absence of covalent crosslinking of the film, affected cell behavior .…”

Section: Mechanotransduction In Viscoelastic Materialsmentioning

confidence: 99%

“…An earlier report showed that their viscoelastic behavior, beside granting them the ability to self‐heal after stretching in the absence of covalent crosslinking of the film, affected cell behavior . This was further addressed by Chester and co‐workers, who designed a family of layer‐by‐layer microgel thin films with similar elastic modulus (≈107 kPa) but decreasing loss tangent (from 1.8 to 0.8) by tuning the internal crosslinking of the particles . The loss tangent of the films was found to be the main regulator in fibroblast migration on these viscoelastic films: on more dissipative substrates, an increase in ROCK activity prompted amoeboid migration, with ellipsoid cells loosely attached to the substrate.…”

Section: Mechanotransduction In Viscoelastic Materialsmentioning

confidence: 99%

The Plot Thickens: The Emerging Role of Matrix Viscosity in Cell Mechanotransduction

Cantini

Donnelly

Dalby

et al. 2019

Adv Healthcare Materials

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Cell mechanotransduction is an area of intense research focus. Until now, very limited tools have existed to study how cells respond to changes in the extracellular matrix beyond, for example, mechanical deformation studies and twisting cytometry. However, emerging are a range of elastic, viscoelastic and even purely viscous materials that deform and dissipate on cellular length and timescales. This article reviews developments in these materials, typically translating from 2D model surfaces to 3D microenvironments and explores how cells interact with them. Specifically, it focuses on emerging concepts such as the molecular clutch model, how different extracellular matrix proteins engage the clutch under viscoelastic‐stress relaxation conditions, and how mechanotransduction can drive transcriptional control through regulators such as YAP/TAZ.

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Surface‐Bound Microgels for Separation, Sensing, and Biomedical Applications

Cutright

Harris

Ramesh

et al. 2021

Adv Funct Materials

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This study presents a comprehensive survey of microgel-coated materials and their functional behavior, describing the complex interplay between the physicochemical and mechanical properties of the microgels and the chemical and morphological features of substrates. The cited literature is articulated in four main sections: i) properties of 2D and 3D substrates, ii) synthesis, modification, and characterization of the microgels, iii) deposition techniques and surface patterning, and iv) application of microgel-coated surfaces focusing on separations, sensing, and biomedical applications. Each section discussesby way of principles and examples -how the various design parameters work in concert to deliver functionality to the composite systems. The case studies presented herein are viewed through a multi-scale lens. At the molecular level, the surface chemistry and the monomer make-up of the microgels endow responsiveness to environmental and artificial physical and chemical cues. At the micro-scale, the response effects shifts in size, mechanical, and optical properties, and affinity towards species in the surrounding liquid medium, ranging from small molecules to cells. These phenomena culminate at the macro-scale in measurable, reversible, and reproducible effects, aiming in a myriad of directions, from lab-scale to industrial applications.

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Viscoelastic properties of microgel thin films control fibroblast modes of migration and pro-fibrotic responses

Cited by 32 publications

References 55 publications

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

The Plot Thickens: The Emerging Role of Matrix Viscosity in Cell Mechanotransduction

Surface‐Bound Microgels for Separation, Sensing, and Biomedical Applications

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