Cell Migration: Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation (Adv. Sci. 2/2017)

Werner, Maike; Blanquer, Sébastien; Haimi, Suvi; Korus, Gabriela; Dunlop, John; Duda, Georg N.; Grijpma, Dirk W.; Petersen, Ansgar

doi:10.1002/advs.201770007

Cited by 7 publications

(4 citation statements)

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“…12,48 This void space in granular hydrogels allows cells to sense and respond to variations in biophysical and biochemical features of constituent microgels to achieve desirable cell responses such as stem cell differentiation and matrix deposition. 6,49,50 For example, cells respond to the surface curvature of spherical microgels by changing migration speed and gene expression, 30,51 which would be altered at the interface of the polygonal microgel shape and resulting pore architecture of EF granular hydrogels when compared to MD and BE hydrogels. Further tuning of granular hydrogel porosity by modifying microgel size or shape, or by modifying the processing into granular hydrogels to alter the packing density may expand the range of currently achievable pore sizes and void fractions to alter cellular interactions.…”

Section: Resultsmentioning

confidence: 99%

“…Although not explored in this study, the ability to tune porosity and pore characteristics, such as through the jamming technique (e.g., vacuum pressure, time of jamming), can have important implications for applying these granular hydrogels toward cell-driven tissue repair. In general, granular hydrogels support cell spreading and proliferation in vitro, and guide infiltration of cells and biological structures from surrounding tissue in vivo. , This void space in granular hydrogels allows cells to sense and respond to variations in biophysical and biochemical features of constituent microgels to achieve desirable cell responses such as stem cell differentiation and matrix deposition. ,, For example, cells respond to the surface curvature of spherical microgels by changing migration speed and gene expression, , which would be altered at the interface of the polygonal microgel shape and resulting pore architecture of EF granular hydrogels when compared to MD and BE hydrogels. Further tuning of granular hydrogel porosity by modifying microgel size or shape, or by modifying the processing into granular hydrogels to alter the packing density may expand the range of currently achievable pore sizes and void fractions to alter cellular interactions. , …”

Section: Results and Discussionmentioning

confidence: 99%

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Influence of Microgel Fabrication Technique on Granular Hydrogel Properties

Muir

Qazi

Shan

et al. 2021

ACS Biomater. Sci. Eng.

107

141

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Bulk hydrogels traditionally used for tissue engineering and drug delivery have numerous limitations, such as restricted injectability and a nanoscale porosity that reduces cell invasion and mass transport. An evolving approach to address these limitations is the fabrication of hydrogel microparticles (i.e., “microgels”) that can be assembled into granular hydrogels. There are numerous methods to fabricate microgels; however, the influence of the fabrication technique on granular hydrogel properties is unexplored. Herein, we investigated the influence of three microgel fabrication techniques (microfluidic devices (MD), batch emulsions (BE), and mechanical fragmentation by extrusion (EF)) on the resulting granular hydrogel properties (e.g., mechanics, porosity, and injectability). Hyaluronic acid (HA) modified with various reactive groups (i.e., norbornenes (NorHA), pentenoates (HA-PA), and methacrylates (MeHA)) were used to form microgels with an average diameter of ∼100 μm. The MD method resulted in homogeneous spherical microgels, the BE method resulted in heterogeneous spherical microgels, and the EF method resulted in heterogeneous polygonal microgels. Across the various reactive groups, microgels fabricated with the MD and BE methods had lower functional group consumption when compared to microgels fabricated with the EF method. When microgels were jammed into granular hydrogels, the storage modulus (G′) of EF granular hydrogels (∼1000–3000 Pa) was consistently an order of magnitude higher than G′ for MD and BE granular hydrogels (∼50–200 Pa). Void space was comparable across all groups, although EF granular hydrogels exhibited an increased number of pores and decreased average pore size when compared to MD and BE granular hydrogels. Furthermore, granular hydrogel properties were tuned by varying the amount of cross-linker used during microgel fabrication. Lastly, granular hydrogels were injectable across formulations due to their general shear-thinning and self-healing properties. Taken together, this work thoroughly characterizes the influence of the microgel fabrication technique on granular hydrogel properties to inform the design of future systems for biomedical applications.

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Section: Resultsmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

Influence of Microgel Fabrication Technique on Granular Hydrogel Properties

Muir

Qazi

Shan

et al. 2021

ACS Biomater. Sci. Eng.

107

141

View full text Add to dashboard Cite

show abstract

“…[6][7][8] Furthermore, the mechanical properties of hydrogel materials, including stiffness, elasticity, and viscoelastic properties, impact the differentiation of mesenchymal stem cells as well as tissue regeneration. [9][10][11][12][13] Hydrogel geometries and surface curvature also influence cell morphology and migration, thus providing additional materials handles for regulating gene expression and cell functions, [14,15] independently of bulk mechanical properties. These studies together indicate the importance of engineering hydrogel microstructures with independently tunable microscale structure and micromechanical properties for controlling cell behavior.…”

Section: Doi: 101002/advs201701010mentioning

confidence: 99%

“…An understanding of the compositions of the two phases as a function of the initial concentrations of RLP and PEG permits determination of the binodal curves and tie lines, which then affords opportunities to predict phase compositions and relative phase volumes as a function of initial solution compositions. The coexistence curve for RLP-6Ac/PEG-4Ac solutions of different initial concentrations (10,15, and 20 wt%) was constructed from the equilibrium concentrations of the individual separated bulk phases from 50/50 RLP-6Ac/PEG-4Ac solutions determined via 1 H NMR as previously reported. [42] Adv.…”

Section: Liquid-liquid Phase Separation Of Rlp-ac/peg-ac Solutionsmentioning

confidence: 99%

Microstructured Elastomer‐PEG Hydrogels via Kinetic Capture of Aqueous Liquid–Liquid Phase Separation

et al. 2018

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Heterogeneous hydrogels with desired matrix complexity are studied for a variety of biomimetic materials. Despite the range of such microstructured materials described, few methods permit independent control over microstructure and microscale mechanics by precisely controlled, single‐step processing methods. Here, a phototriggered crosslinking methodology that traps microstructures in liquid–liquid phase‐separated solutions of a highly elastomeric resilin‐like polypeptide (RLP) and poly(ethylene glycol) (PEG) is reported. RLP‐rich domains of various diameters can be trapped in a PEG continuous phase, with the kinetics of domain maturation dependent on the degree of acrylation. The chemical composition of both hydrogel phases over time is assessed via in situ hyperspectral coherent Raman microscopy, with equilibrium concentrations consistent with the compositions derived from NMR‐measured coexistence curves. Atomic force microscopy reveals that the local mechanical properties of the two phases evolve over time, even as the bulk modulus of the material remains constant, showing that the strategy permits control of mechanical properties on micrometer length scales, of relevance in generating mechanically robust materials for a range of applications. As one example, the successful encapsulation, localization, and survival of primary cells are demonstrated and suggest the potential application of phase‐separated RLP‐PEG hydrogels in regenerative medicine applications.

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Curvotaxis directs cell migration through cell-scale curvature landscapes

Pieuchot¹,

Marteau²,

Guignandon³

et al. 2018

Nat Commun

233

222

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Cells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term “curvotaxis” that enables the cells to respond to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton—the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue.

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Cell Migration: Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation (Adv. Sci. 2/2017)

Cited by 7 publications

References 0 publications

Influence of Microgel Fabrication Technique on Granular Hydrogel Properties

Influence of Microgel Fabrication Technique on Granular Hydrogel Properties

Microstructured Elastomer‐PEG Hydrogels via Kinetic Capture of Aqueous Liquid–Liquid Phase Separation

Curvotaxis directs cell migration through cell-scale curvature landscapes

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