Large-scale curvature sensing by epithelial monolayers depends on active cell mechanics and nuclear mechanoadaptation

2020 ◽  
Author(s):  
Grace Lim
Keyword(s):  
Cell Mechanics ◽  
Large Scale ◽  
Active Cell ◽  
Curvature Sensing ◽  
Epithelial Monolayers

scholarly journals Large-scale curvature sensing by epithelial monolayers depends on active cell mechanics and nuclear mechanoadaptation

2020 ◽  
Author(s):  
Marine Luciano ◽  
Shi-Lei Xue ◽  
Winnok H. De Vos ◽  
Lorena Redondo Morata ◽  
Mathieu Surin ◽  
...  
Keyword(s):  
Cell Mechanics ◽  
Large Scale ◽  
Chromatin Condensation ◽  
Active Cell ◽  
Epithelial Tissue ◽  
Hippo Signaling ◽  
Curvature Sensing ◽  
Epithelial Monolayers ◽  
Substrate Curvature

AbstractWhile many tissues fold in vivo in a highly reproducible and robust way, epithelial folds remain difficult to reproduce in vitro, so that the effects and underlying mechanisms of local curvature on the epithelial tissue remains unclear. Here, we photoreticulated polyacrylamide hydrogels though an optical photomask to create corrugated hydrogels with isotropic wavy patterns, allowed us to show that concave and convex curvatures affect cellular and nuclear shape. By culturing MDCK epithelial cells at confluency on corrugated hydrogels, we showed that the substrate curvature leads to thicker epithelial zones in the valleys and thinner ones on the crest, as well as corresponding density, which can be generically explained by a simple 2D vertex model, leading us to hypothesize that curvature sensing could arise from resulting density/thickness changes. Additionally, positive and negative local curvatures lead to significant modulations of the nuclear morphology and positioning, which can also be well-explained by an extension of vertex models taking into account membrane-nucleus interactions, where thickness/density modulation generically translate into the corresponding changes in nuclear aspect ratio and position, as seen in the data. Consequently, we find that the spatial distribution of Yes associated proteins (YAP), the main transcriptional effector of the Hippo signaling pathway, is modulated in folded epithelial tissues according to the resulting thickness modulation, an effect that disappears at high cell density. Finally, we showed that these deformations are also associated with changes of A-type and B-type lamin expression, significant chromatin condensation and to lower cell proliferation rate. These findings show that active cell mechanics and nuclear mechanoadaptation are key players of the mechanistic regulation of epithelial monolayers to substrate curvature, with potential application for a number of in vivo situations.

scholarly journals Shh induces symmetry breaking in the presomitic mesoderm by inducing tissue shear and orientated cell rearrangements

2019 ◽  
Author(s):  
J. Yin ◽  
T. E. Saunders
Keyword(s):  
Skeletal Muscle ◽  
Symmetry Breaking ◽  
Cell Mechanics ◽  
Large Scale ◽  
Cell Layer ◽  
Cell Populations ◽  
Presomitic Mesoderm ◽  
Cellular Changes ◽  
Muscle Myosin ◽  
Adaxial Cells

AbstractFuture boundaries of skeletal muscle segments are determined in the presomitic mesoderm (PSM). Within the PSM, future somitic cells undergo significant changes in both morphology and position. How such large-scale cellular changes are coordinated and the effect on the future border formation is unknown. We find that cellular rearrangements differ between cell populations within the PSM. In contrast to lateral somitic cells, which display less organized rearrangement, the adaxial cell layer undergoes significant tissue shearing with dorsal and ventral cells sliding posteriorly. This shear is generated by orientated intercalations of dorsally and ventrally located adaxial cells, which induces a chevron-like pattern. We find Shh signaling is required for the tissue shear and morphogenesis of adaxial cells. In particular, we observe Shh-dependent polarized recruitment of non-muscle myosin IIA drives apical constrictions, and thus the intercalations and shear. This reveals a novel role for Shh in regulating cell mechanics in the PSM.

scholarly journals Large-scale curvature sensing by directional actin flow drives cellular migration mode switching

2019 ◽  
Vol 15 (4) ◽  
pp. 393-402 ◽  
Author(s):  
Tianchi Chen ◽  
Andrew Callan-Jones ◽  
Eduard Fedorov ◽  
Andrea Ravasio ◽  
Agustí Brugués ◽  
...  
Keyword(s):  
Large Scale ◽  
Cellular Migration ◽  
Mode Switching ◽  
Curvature Sensing

scholarly journals Proteomic Analysis of the Intestinal Epithelial Cell Response to EnteropathogenicEscherichia coli

2004 ◽  
Vol 279 (19) ◽  
pp. 20127-20136 ◽  
Author(s):  
Philip R. Hardwidge ◽  
Isabel Rodriguez-Escudero ◽  
David Goode ◽  
Sam Donohoe ◽  
Jimmy Eng ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Cellular Response ◽  
Large Scale ◽  
Cell Types ◽  
Effector Proteins ◽  
Intestinal Epithelial ◽  
Host Proteins ◽  
Epithelial Monolayers ◽  
Childhood Morbidity ◽  
Biochemical Analyses

We present the first large scale proteomic analysis of a human cellular response to a pathogen. EnteropathogenicEscherichia coli(EPEC) is an enteric human pathogen responsible for much childhood morbidity and mortality worldwide. EPEC uses a type III secretion system (TTSS) to inject bacterial proteins into the cytosol of intestinal epithelial cells, resulting in diarrhea. We analyzed the host response to TTSS-delivered EPEC effector proteins by infecting polarized intestinal epithelial monolayers with either wild-type or TTSS-deficient EPEC. Host proteins were isolated and subjected to quantitative profiling using isotope-coded affinity tagging (ICAT) combined with electrospray ionization tandem mass spectrometry. We identified over 2000 unique proteins from infected Caco-2 monolayers, of which ∼13% are expressed differentially in the presence of TTSS-delivered EPEC effector proteins. We validated these datain silicoand through immunoblotting and immunofluorescence microscopy. The identified changes extend cytoskeletal observations made in less relevant cell types and generate testable hypotheses with regard to host proteins potentially involved in EPEC-induced diarrhea. These data provide a framework for future biochemical analyses of host-pathogen interactions.

scholarly journals Microtopographical guidance of macropinocytic signaling patches

2021 ◽  
Vol 118 (50) ◽  
pp. e2110281118
Author(s):  
Gen Honda ◽  
Nen Saito ◽  
Taihei Fujimori ◽  
Hidenori Hashimura ◽  
Mitsuru J. Nakamura ◽  
...  
Keyword(s):  
Immune Cells ◽  
Large Scale ◽  
Nanometer Scale ◽  
Distinct Mode ◽  
Structured Surfaces ◽  
Curvature Sensing ◽  
Quantitative Image ◽  
Membrane Protrusions ◽  
Particle Ingestion ◽  
Micrometer Scale

In fast-moving cells such as amoeba and immune cells, dendritic actin filaments are spatiotemporally regulated to shape large-scale plasma membrane protrusions. Despite their importance in migration, as well as in particle and liquid ingestion, how their dynamics are affected by micrometer-scale features of the contact surface is still poorly understood. Here, through quantitative image analysis of Dictyostelium on microfabricated surfaces, we show that there is a distinct mode of topographical guidance directed by the macropinocytic membrane cup. Unlike other topographical guidance known to date that depends on nanometer-scale curvature sensing protein or stress fibers, the macropinocytic membrane cup is driven by the Ras/PI3K/F-actin signaling patch and its dependency on the micrometer-scale topographical features, namely PI3K/F-actin–independent accumulation of Ras-GTP at the convex curved surface, PI3K-dependent patch propagation along the convex edge, and its actomyosin-dependent constriction at the concave edge. Mathematical model simulations demonstrate that the topographically dependent initiation, in combination with the mutually defining patch patterning and the membrane deformation, gives rise to the topographical guidance. Our results suggest that the macropinocytic cup is a self-enclosing structure that can support liquid ingestion by default; however, in the presence of structured surfaces, it is directed to faithfully trace bent and bifurcating ridges for particle ingestion and cell guidance.

scholarly journals Myosin II controls junction fluctuations to guide epithelial tissue ordering

2016 ◽  
Author(s):  
Scott Curran ◽  
Charlotte Strandkvist ◽  
Jasper Bathmann ◽  
Marc de Gennes ◽  
Alexandre Kabla ◽  
...  
Keyword(s):  
Large Scale ◽  
Gradual Increase ◽  
Computational Modelling ◽  
Steady Increase ◽  
Epithelial Tissue ◽  
Epithelial Monolayers ◽  
Tissue Integrity ◽  
Stochastic Fluctuations ◽  
The Face ◽  
Dynamic Structures

AbstractHomophilic interactions between E-Cadherin molecules generate adhesive interfaces or junctions (AJs) that connect neighbouring cells in epithelial monolayers. These are highly dynamic structures. Under conditions of homeostasis, changes in the length of individual interfaces provide epithelia with the fluidity required to maintain tissue integrity in the face of cell division, delamination and extrinsic forces. Furthermore, when acted upon by polarized actomyosin-based forces, changes in AJ length can also drive neighbour exchange to reshape an entire tissue. Whilst the contribution of AJ remodelling to developmental morphogenesis has been subjected to intensive study, less is known about AJ dynamics in other circumstances. Here, using a combination of experiment and computational modelling, we study AJ dynamics in an epithelium that undergoes a gradual increase in packing order without concomitant large-scale changes in tissue shape or size. Under these conditions, we find that neighbour exchange events are driven by stochastic fluctuations in junction length, which are regulated at least in part by the level of junctional actomyosin. As a result of this behaviour, the steady increase in junctional actomyosin and consequent tension that accompanies development steadily reduces the rate of neighbour exchange and orders the tissue. This leads us to propose a model in which topological transitions, that underpin tissue fluidity, are either inhibited or biased by actomyosin-based forces, to drive, respectively, tissue ordering or deformation.

scholarly journals Active cell mechanics: Measurement and theory

2015 ◽  
Vol 1853 (11) ◽  
pp. 3083-3094 ◽  
Author(s):  
Wylie W. Ahmed ◽  
Étienne Fodor ◽  
Timo Betz
Keyword(s):  
Cell Mechanics ◽  
Active Cell

scholarly journals Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Tiankai Zhao ◽  
Yao Zhang ◽  
Qiong Wei ◽  
Xuechen Shi ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Active Cell ◽  
Epithelial Monolayers ◽  
Cell Matrix
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