Holding it together: when cadherin meets cadherin

Arslan, Feyza Nur; Eckert, Julia; Schmidt, Thomas; Heisenberg, Carl‐Philipp

doi:10.1016/j.bpj.2021.03.025

Cited by 39 publications

(26 citation statements)

References 131 publications

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“…Mechanical cues from the microenvironment modulate vascular endothelium permeability and ECM synthesis. Stresses from the microenvironment are then translated to adhesion forces created between cells, and cellular traction forces applied on the ECM (Arslan et al, 2021;Lemmon et al, 2005). Traction forces generated by the actomyosin machinery contribute to the cellular mechanical properties, and they are believed to play pivotal roles in regulating various cellular mechanosensing processes, such as cell differentiation, migration and proliferation.…”

Section: Introductionmentioning

confidence: 99%

Single cell micro-pillar-based characterization of endothelial and fibroblast cell mechanics

Eckert

Abouleila

Schmidt

et al. 2021

Preprint

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Mechanotransduction, the ability of cells to sense and respond to the mechanical cues from their microenvironment, plays an important role in numerous cellular processes, ranging from cell migration to differentiation. Several techniques have been developed to investigate the underlying mechanisms of mechanotransduction, in particular, force measurement-based techniques. However, we still lack basic single cell quantitative comparison on the mechanical properties of commonly used cell types, such as endothelial and fibroblast cells. Such information is critical to provide a precedent for studying complex tissues and organs that consist of various cell types. In this short communication, we report on the mechanical characterization of the commonly used endothelial and fibroblast cells at the single cell level. Using a micropillar-based assay, we measured the traction force profiles of these cells. Our study showcases differences between the two cell types in their traction force distribution and morphology. The results reported can be used as a reference and to lay the groundwork for future analysis of numerous disease models involving these cells.

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Section: Introductionmentioning

confidence: 99%

Single cell micro-pillar-based characterization of endothelial and fibroblast cell mechanics

Eckert

Abouleila

Schmidt

et al. 2021

Preprint

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“…Relevant mechanical stimuli for cadherins in vivo are expected to be diverse (98)(99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110). As cells divide and tissues develop, cell-cell contacts will be experiencing tension.…”

Section: Discussionmentioning

confidence: 99%

Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes

Neel

Nisler

Walujkar

et al. 2021

Preprint

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Cadherins are a superfamily of adhesion proteins involved in a variety of biological processes that include the formation of intercellular contacts, the maintenance of tissue integrity, and the development of neuronal circuits. These transmembrane proteins are characterized by ectodomains composed of a variable number of extracellular cadherin (EC) repeats that are similar but not identical in sequence and fold. E-cadherin, along with desmoglein and desmocollin proteins, are three classical-type cadherins that have slightly curved ectodomains and engage in homophilic and heterophilic interactions through an exchange of conserved tryptophan residues in their N-terminal EC1 repeat. In contrast, clustered protocadherins are straighter than classical cadherins and interact through an antiparallel homophilic binding interface that involves overlapped EC1 to EC4 repeats. Here we present molecular dynamics simulations that model the adhesive domains of these cadherins using available crystal structures, with systems encompassing up to 2.8 million atoms. Simulations of complete classical cadherin ectodomain dimers predict a two-phased elastic response to force in which these complexes first softly unbend and then stiffen to unbind without unfolding. Simulated α, β, and γ clustered protocadherin homodimers lack a two-phased elastic response, are brittle and stiffer than classical cadherins, and exhibit complex unbinding pathways that in some cases involve transient intermediates. We propose that these distinct mechanical responses are important for function, with classical cadherin ectodomains acting as molecular shock absorbers and with stiffer clustered protocadherin ectodomains facilitating overlap that favors binding specificity over mechanical resilience. Overall, our simulations provide insights into the molecular mechanics of single cadherin dimers relevant in the formation of cellular junctions essential for tissue function.

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“…The classical cadherin Cdh3 (aka C-cadherin; aka mammalian P-cadherin) plays a crucial role in morphogenesis of the dorsal marginal zone (DMZ) mesoderm of the Xenopus gastrula (Fagotto et al, 2013;Huebner et al, 2021;Lee and Gumbiner, 1995;Pfister et al, 2016), a powerful and deeply studied paradigm for understanding CE (Keller and Sutherland, 2020). Cadherins control numerous cellular processes including proliferation, cell migration, cell polarity, and mechanotransduction and to achieve this assortment of cellular tasks, cadherins interact with an array of structural and signaling molecules (Arslan et al, 2021). However, we currently lack a comprehensive roster of proteins interacting with Cdh3 in the Xenopus DMZ.…”

Section: Identification Of Tissue and Stage Specific Cdh3 Protein Interactions In Xenopus Convergent Extensionmentioning

confidence: 99%

Cell adhesions link subcellular actomyosin dynamics to tissue scale force production during vertebrate convergent extension

Huebner

Weng

et al. 2021

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Axis extension is a fundamental biological process that shapes multicellular organisms. The design of the animal body plan is encoded in the genome and execution of this program is a multiscale mechanical progression involving the coordinated movement of proteins, cells, and whole tissues. Thus, a key challenge to understanding axis extension is connecting events that occur across these various length scales. Here, we use approaches from proteomics, cell biology, and tissue biomechanics to describe how a poorly characterized cell adhesion effector, the Armadillo Repeat protein deleted in Velo-Cardio-Facial syndrome (Arvcf) catenin, controls vertebrate head-to-tail axis extension. We find that Arvcf catenin is required for axis extension within the intact organism but is not required for extension of isolated tissues. We then show that the organism scale phenotype is caused by a modest defect in force production at the tissue scale that becomes apparent when the tissue is challenged by external resistance. Finally, we show that the tissue scale force defect results from dampening of the pulsatile recruitment of cell adhesion and cytoskeletal proteins to cell membranes. These results not only provide a comprehensive understanding of Arvcf function during an essential biological process, but also provide insight into how a modest cellular scale defect in cell adhesion results in an organism scale failure of development.

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Holding it together: when cadherin meets cadherin

Cited by 39 publications

References 131 publications

Single cell micro-pillar-based characterization of endothelial and fibroblast cell mechanics

Single cell micro-pillar-based characterization of endothelial and fibroblast cell mechanics

Elastic versus Brittle Mechanical Responses Predicted for Dimeric Cadherin Complexes

Cell adhesions link subcellular actomyosin dynamics to tissue scale force production during vertebrate convergent extension

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