Three-dimensional traction forces of Schwann cells on compliant substrates

López-Fagundo, Cristina; Bar-Kochba, Eyal; Livi, Liane L.; Hoffman–Kim, Diane; Franck, Christian

doi:10.1098/rsif.2014.0247

Cited by 39 publications

(37 citation statements)

References 42 publications

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“…out of plane) correlates with the weakest adhesion and shortest bond lifetime, and formation of such bonds may correlate with rapid motility (36,37). This model of rapid motility is in contrast to the situation for the adhesion of mesenchymal cells, which form a relatively even distribution of in-plane and out-of-plane tractions but adhere more tightly and move more slowly (16,38).…”

Section: Discussionmentioning

confidence: 83%

Matrix Confinement Plays a Pivotal Role in Regulating Neutrophil-generated Tractions, Speed, and Integrin Utilization

Toyjanova

Flores-Cortez

Reichner

et al. 2015

Journal of Biological Chemistry

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Background: Neutrophils must generate well regulated forces to migrate within the confined, three-dimensional space of diseased tissues. Results: Spatial confinement induces a switch to integrin-independent motility, but integrins regulate three-dimensional traction force generation. Conclusion: Physical confinement is sufficient to induce integrin-independent motility. Significance: Spatially confined double hydrogels are a biomimetic system that may allow for ex vivo testing of neutrophilspecific therapeutics.

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Section: Discussionmentioning

confidence: 83%

Matrix Confinement Plays a Pivotal Role in Regulating Neutrophil-generated Tractions, Speed, and Integrin Utilization

Toyjanova

Flores-Cortez

Reichner

et al. 2015

Journal of Biological Chemistry

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“…For example, in very compliant collagen 3D matrices, fibroblasts have a dendritic network of extensions; while in comparably stiffer and constrained matrices, fibroblasts have stellate or bipolar shape . For Schwann cells, when seeding the cells on top of a substrate (2D) with elastic modulus ranging from 0.24 to 4.80 kPa, most cells exhibited bipolar shape and a mature actin cytoskeleton was observed . However, the area of cell spreading was relatively insensitive to substrate stiffness in this range.…”

Section: Resultsmentioning

confidence: 99%

“…Researchers have also shown that differences exist between stiffnesses that support neuronal cells compared to glial cells . Specifically for Schwann cells, researchers used 2D substrates, such as polyacrylamide gels, to investigate how the Schwann cell response was affected by stiffness . However, in clinical practice, Schwann cells would not reside on a material, but rather inside a scaffold, and it has been shown that the cell response to stiffness in 2D does not match the response in 3D.…”

Section: Introductionmentioning

confidence: 99%

Tuning the Mechanical Properties of Poly(Ethylene Glycol) Microgel‐Based Scaffolds to Increase 3D Schwann Cell Proliferation

Zhou

Stukel

Cebull

et al. 2016

Macromolecular Bioscience

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2D in vitro studies have demonstrated that Schwann cells prefer scaffolds with mechanical modulus approximately 10× higher than the modulus preferred by nerves, limiting the ability of many scaffolds to promote both neuron extension and Schwann cell proliferation. Therefore, the goals of this work are to develop and characterize microgel-based scaffolds that are tuned over the stiffness range relevant to neural tissue engineering and investigate Schwann cell morphology, viability, and proliferation within 3D scaffolds. Using thiol-ene reaction, microgels with surface thiols are produced and crosslinked into hydrogels using a multiarm vinylsulfone (VS). By varying the concentration of VS, scaffold stiffness ranges from 0.13 to 0.76 kPa. Cell morphology in all groups demonstrates that cells are able to spread and interact with the scaffold through day 5. Although the viability in all groups is high, proliferation of Schwann cells within the scaffold of G* = 0.53 kPa is significantly higher than other groups. This result is ≈ 5× lower than previously reported optimal stiffnesses on 2D surfaces, demonstrating the need for correlation of 3D cell response to mechanical modulus. As proliferation is the first step in Schwann cell integration into peripheral nerve conduits, these scaffolds demonstrate that the stiffness is a critical parameter to optimizing the regenerative process.

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“…Whereas the FIDVC natively provides a detailed fullfield map of the entire matrix displacements in the vicinity of the cell, many practical applications require simpler biomechanical classification metrics. In traditional TFM studies, these metrics include simple scalar quantities such as root-mean-squared tractions, total forces, strain energies, and contractility measures such as the trace of the dipole tensor (7,15,18,36). However, computation of these metrics requires the constitutive behavior of the matrix.…”

Section: Mdmmentioning

confidence: 99%

“…Analysis of cellular force generation, and its role in regulating homeostasis across a variety of cellular phenotypes and experimental platforms, has received much attention over the last three decades (7)(8)(9)(10)(11)(12)(13). Experimental quantification of cellular forces has produced several cell traction measurement techniques, ranging from surface wrinkle detection and flexure of micropillars to traction force microscopy (TFM) (12,(14)(15)(16)(17)(18)(19)(20).…”

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confidence: 99%

Mean deformation metrics for quantifying 3D cell–matrix interactions without requiring information about matrix material properties

Stout

Bar-Kochba

Estrada

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mechanobiology relates cellular processes to mechanical signals, such as determining the effect of variations in matrix stiffness with cell tractions. Cell traction recorded via traction force microscopy (TFM) commonly takes place on materials such as polyacrylamideand polyethylene glycol-based gels. Such experiments remain limited in physiological relevance because cells natively migrate within complex tissue microenvironments that are spatially heterogeneous and hierarchical. Yet, TFM requires determination of the matrix constitutive law (stress-strain relationship), which is not always readily available. In addition, the currently achievable displacement resolution limits the accuracy of TFM for relatively small cells. To overcome these limitations, and increase the physiological relevance of in vitro experimental design, we present a new approach and a set of associated biomechanical signatures that are based purely on measurements of the matrix's displacements without requiring any knowledge of its constitutive laws. We show that our mean deformation metrics (MDM) approach can provide significant biophysical information without the need to explicitly determine cell tractions. In the process of demonstrating the use of our MDM approach, we succeeded in expanding the capability of our displacement measurement technique such that it can now measure the 3D deformations around relatively small cells (∼10 micrometers), such as neutrophils. Furthermore, we also report previously unseen deformation patterns generated by motile neutrophils in 3D collagen gels.traction force microscopy | confocal microscopy | large deformations | neutrophil M echanical cues within the cellular microenvironment regulate numerous fundamental functions including cell adhesion, deformation, and generation of traction (1-6). Analysis of cellular force generation, and its role in regulating homeostasis across a variety of cellular phenotypes and experimental platforms, has received much attention over the last three decades (7-13). Experimental quantification of cellular forces has produced several cell traction measurement techniques, ranging from surface wrinkle detection and flexure of micropillars to traction force microscopy (TFM) (12,(14)(15)(16)(17)(18)(19)(20). In TFM, measured cell-induced displacements are converted into tractions using various mathematical frameworks (14,15,17,18,21,22). Both twoand 3D TFM techniques have steadily increased in sophistication and now feature high-spatial displacement resolution and advanced computational formalisms to connect this displacement information to complex material constitutive laws (17,23,24).To successfully perform TFM, it is critical to know the stressstrain constitutive behavior of the matrix surrounding the cell. Although many TFM substrates feature relatively simple artificial gel constructs, such as polyacrylamide and polyethylene glycol, these constructs are impenetrable by cells and obviate measures obtained while cells are in a 3D setting (as would be the case within a bodily ...

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Three-dimensional traction forces of Schwann cells on compliant substrates

Cited by 39 publications

References 42 publications

Matrix Confinement Plays a Pivotal Role in Regulating Neutrophil-generated Tractions, Speed, and Integrin Utilization

Matrix Confinement Plays a Pivotal Role in Regulating Neutrophil-generated Tractions, Speed, and Integrin Utilization

Tuning the Mechanical Properties of Poly(Ethylene Glycol) Microgel‐Based Scaffolds to Increase 3D Schwann Cell Proliferation

Mean deformation metrics for quantifying 3D cell–matrix interactions without requiring information about matrix material properties

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