Neurite branching on deformable substrates

Flanagan, Lisa A.; Ju, Yo‐El S.; Marg, Beatrice; Osterfield, Miriam; Janmey, Paul A.

doi:10.1097/00001756-200212200-00007

Cited by 680 publications

(654 citation statements)

References 30 publications

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“…These findings are consistent with previous observations (Engler et al, 2004;Flanagan et al, 2002), but beg the question of how rigidity was detected by the neurons. Two major models are suggested: first, the mechanism of rigidity sensing involves different molecular components, similar to the different response pathways for FN and collagen rigidity (Kostic and Sheetz, 2006;Wang et al, 2001); second, the sensing mechanism is the same in fibroblasts and neurons but the response to the sensory signal could be different.…”

Section: Discussionsupporting

confidence: 93%

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RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

Kostić

Sap

Sheetz

2007

Journal of Cell Science

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Receptor-like protein tyrosine phosphatase α (RPTPα)-knockout mice have severe hippocampal abnormalities similar to knockouts of the Src family kinase Fyn. These enzymes are linked to the matrix-rigidity response in fibroblasts, but their function in neurons is unknown. The matrix-rigidity response of fibroblasts appears to differ from that of neuronal growth cones but it is unknown whether the rigidity detection mechanism or response pathway is altered. Here, we report that RPTPα is required for rigidity-dependent reinforcement of fibronectin (FN)-cytoskeleton bonds and the rigidity response in hippocampal neuron growth cones, like in fibroblasts. In control neurons, rigid FN surfaces inhibit neurite extension and neuron differentiation relative to soft surfaces. In RPTPα–/– neurons, no inhibition of extension and differentiation is found on both rigid and soft surfaces. The RPTPα-dependent rigidity response in neurons is FN-specific, and requires clustering of αvβ6 integrin at the leading edge of the growth cones. Further, RPTPα is necessary for the rigidity-dependent concentration of Fyn and p130Cas phosphorylation at the leading edge of the growth cone, like it is in fibroblasts. Although neurons respond to rigid FN surfaces in the opposite way to fibroblasts, we suggest that the mechanism of detecting FN rigidity is similar and involves rigidity-dependent RPTPα recruitment of Fyn.

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Section: Discussionsupporting

confidence: 93%

“…Several recent studies have shown that soft substrates stimulated neurite extension and branching, but inhibited glial cell growth (Balgude et al, 2001;Engler et al, 2004;Flanagan et al, 2002;Georges et al, 2006;Lamoureux et al, 2002;Strassman et al, 1973). However, mechanisms of this regulation are not clear.…”

Section: Introductionmentioning

confidence: 99%

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

Kostić

Sap

Sheetz

2007

Journal of Cell Science

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“…It has previously been demonstrated that the layer of matrix protein does not alter the overall stiffness of the system, that these concentrations of matrix protein allow maximal cell adhesion, and that cells deposit minimal amounts of additional matrix on the supports. 25,33 Microscopy and Morphological Measurements. Phase-contrast images of cells were taken using an inverted microscope with IPLab software (Scanalytics, Fairfax, VA) and a Hamamatsu digital camera.…”

Section: Methodsmentioning

confidence: 99%

Transforming growth factor-β and substrate stiffness regulate portal fibroblast activation in culture

et al. 2007

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Myofibroblasts derived from portal fibroblasts are important fibrogenic cells in the early stages of biliary fibrosis. In contrast to hepatic stellate cells, portal fibroblasts have not been well studied in vitro, and little is known about their myofibroblastic differentiation. In this article we report the isolation and characterization of rat portal fibroblasts in culture. We demonstrate that primary portal fibroblasts undergo differentiation to ␣-smooth muscle actin-expressing myofibroblasts over 10 -14 days. Marker analysis comparing portal fibroblasts to hepatic stellate cells demonstrated that these are distinct populations and that staining with elastin and desmin can differentiate between them. Portal fibroblasts expressed elastin at all stages in culture but never expressed desmin, whereas hepatic stellate cells consistently expressed desmin but never elastin. Immunostaining of rat liver tissue confirmed these results in vivo. Characterization of portal fibroblast differentiation in culture demonstrated that these cells required transforming growth factor-␤ (TGF-␤): cells remained quiescent in the presence of a TGF-␤ receptor kinase inhibitor, whereas exogenous TGF-␤1 enhanced portal fibroblast ␣-smooth muscle actin expression and stress fiber formation. In contrast, platelet-derived growth factor inhibited myofibroblastic differentiation. Portal fibroblasts were also dependent on mechanical tension for myofibroblastic differentiation, and cells cultured on polyacrylamide supports of variable stiffness demonstrated an increasingly myofibroblastic phenotype as stiffness increased. Conclusion: Portal fibroblasts are morphologically and functionally distinct from hepatic stellate cells. Portal fibroblast myofibroblastic differentiation can be modeled in culture and requires both TGF-␤ and mechanical tension. (HEPATOLOGY 2007;46:1246-1256

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“…In vitro it has been shown that cells when cultured on materials are able to sense mechanical characteristics of the material and respond with a function in dependence on the mechanics [27]. Differentiation of mammary epithelial cells increased on soft collagen gel, as opposed to rigid tissue culture plastics [28], experiments with endothelial cells demonstrated a lower branching of the cellular network on stiffer materials compared with soft substrate [29] and similarly, neurons are branching more on soft material than on a stiff substrate [30]. A role of the stiffness of a material for regenerative processes was convincingly demonstrated when mesenchymal stem cells were cultured on hydrogels with varying stiffnesses [31].…”

Section: Stiffnessmentioning

confidence: 99%

Cell-material interaction

Rychly

Nebe

2013

BioNanoMaterials

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Abstract:The interaction of cells with material surfaces is of fundamental relevance and contributes to the clinical success of implants. Cells sense their physico-chemical environment resulting in focal adhesion reorganization, spatio-temporal localization and activation of integrin dependent signalling proteins as well as phenotypic changes, e.g., of the actin cytoskeleton. The technology of designing instructive biomaterials involves chemical modifications by grafting of chemical groups, adhesion ligands and growth factors. Physical modifications of the materials are created by structuring the surfaces stochastically and geometrically and by modifications of the material stiffness. Insights into the mechanism at the interface that are involved in the regulation of cells such as stem cells, osteoblasts and chondrocytes by materials will advance the development of innovative biomaterials in regenerative medicine.

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Neurite branching on deformable substrates

Cited by 680 publications

References 30 publications

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

Transforming growth factor-β and substrate stiffness regulate portal fibroblast activation in culture

Cell-material interaction

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