Role of the Nucleus as a Sensor of Cell Environment Topography

Anselme, Karine; Wakhloo, Nayana Tusamda; Rougerie, Pablo; Pieuchot, Laurent

doi:10.1002/adhm.201701154

Cited by 55 publications

(42 citation statements)

References 215 publications

(299 reference statements)

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“…The surfaces of biomaterials play a central role in the modulation of cell behavior [42,43] and in mechanotransduction [7,44,45]. Topographical features have an influence on direct transmission of force, which causes a reorganization of the cytoskeleton [31,[46][47][48] and changes in cell shape to adapt to the underlying surface [44,49,50]. Furthermore, signaling pathways ultimately modulate cell proliferation and differentiation [4,5,8,10,46,[51][52][53][54][55].…”

Section: Discussionmentioning

confidence: 99%

ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars—A Combined In Vitro and In Silico Study

Staehlke

Haack

Waldner

et al. 2020

Cells

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The physico-chemical surface design of implants influences the surrounding cells. Osteoblasts on sharp-edged micro-topographies revealed an impaired cell phenotype, function and Ca2+ mobilization. The influence of edges and ridges on the Wnt/β-catenin pathway in combination with the cells’ stress response has not been clear. Therefore, MG-63 osteoblasts were studied on defined titanium-coated micro-pillars (5 × 5 × 5 µm) in vitro and in silico. MG-63s on micro-pillars indicated an activated state of the Wnt/β-catenin pathway. The β-catenin protein accumulated in the cytosol and translocated into the nucleus. Gene profiling indicated an antagonism mechanism of the transcriptional activity of β-catenin due to an increased expression of inhibitors like ICAT (inhibitor of β-catenin and transcription factor-4). Cells on pillars produced a significant reactive oxygen species (ROS) amount after 1 and 24 h. In silico analyses provided a detailed view on how transcriptional activity of Wnt signaling is coordinated in response to the oxidative stress induced by the micro-topography. Based on a coordinated expression of regulatory elements of the Wnt/β-catenin pathway, MG-63s are able to cope with an increased accumulation of β-catenin on micro-pillars and suppress an unintended target gene expression. Further, β-catenin may be diverted into other signaling pathways to support defense mechanisms against ROS.

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Section: Discussionmentioning

confidence: 99%

ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars—A Combined In Vitro and In Silico Study

Staehlke

Haack

Waldner

et al. 2020

Cells

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“…Both nuclei distribution and F-actin orientation satisfy these criteria. Several studies establish nuclei as essential players of cell reaction to topography 38 . We demonstrated that single cells avoid crossing convex regions owing to the tendency of nuclei to slide away from convex curvature 12 .…”

Section: Discussionmentioning

confidence: 99%

Topographical curvature is sufficient to control epithelium elongation

Rougerie

Pieuchot

Santos

et al. 2020

Sci Rep

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How biophysical cues can control tissue morphogenesis is a central question in biology and for the development of efficient tissue engineering strategies. Recent data suggest that specific topographies such as grooves and ridges can trigger anisotropic tissue growth. However, the specific contribution of biologically relevant topographical features such as cell-scale curvature is still unclear. Here we engineer a series of grooves and ridges model topographies exhibiting specific curvature at the ridge/groove junctions and monitored the growth of epithelial colonies on these surfaces. We observe a striking proportionality between the maximum convex curvature of the ridges and the elongation of the epithelium. This is accompanied by the anisotropic distribution of F-actin and nuclei with partial exclusion of both in convex regions as well as the curvature-dependent reorientation of pluricellular protrusions and mitotic spindles. This demonstrates that curvature itself is sufficient to trigger and modulate the oriented growth of epithelia through the formation of convex “topographical barriers” and establishes curvature as a powerful tuning parameter for tissue engineering and biomimetic biomaterial design.

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“…The important influence of geometrical constraints on the evolution and the equilibrium configurations is well accepted in the context of physical systems. The role of geometrical constraints to influence or even to guide biological processes is also starting to emerge [68][69][70][71][72]. In a biological context the role of geometrical constraints goes beyond what was explored for physical systems.…”

Section: Discussionmentioning

confidence: 99%

The Emergence of Complexity from a Simple Model for Tissue Growth

et al. 2019

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The growth of living tissue is known to be modulated by mechanical as well as biochemical signals. We study a simple numerical model where the tissue growth rate depends on a chemical potential describing biochemical and mechanical driving forces in the material. In addition, the growing tissue is able to adhere to a three-dimensional surface and is subjected to surface tension where not adhering. We first show that this model belongs to a wider class of models describing particle growth during phase separation. We then analyse the predicted tissue shapes growing on a solid support corresponding to a cut hollow cylinder, which could be imagined as an idealized description of a broken long bone. We demonstrate the appearance of complex shapes described by Delauney surfaces and reminiscent of the shapes of callus appearing during bone healing. This complexity of shapes arises despite the extreme simplicity of the growth model, as a consequence of the threedimensional boundary conditions imposed by the solid support.

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Role of the Nucleus as a Sensor of Cell Environment Topography

Cited by 55 publications

References 215 publications

ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars—A Combined In Vitro and In Silico Study

ROS Dependent Wnt/β-Catenin Pathway and Its Regulation on Defined Micro-Pillars—A Combined In Vitro and In Silico Study

Topographical curvature is sufficient to control epithelium elongation

The Emergence of Complexity from a Simple Model for Tissue Growth

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