Cell chirality regulates intercellular junctions and endothelial permeability

Fan, Jie; Ray, Poulomi; Lu, Yao Wei; Kaur, Gurleen; Schwarz, John J.; Wan, Leo Q.

doi:10.1126/sciadv.aat2111

Cited by 53 publications

(96 citation statements)

References 50 publications

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“…We found that thalidomide, paroxetine, and methoxamine increased the percentage of counterclockwise (CCW) cells, suggesting a potential role of PKC in cardiac cell chirality (31–34). Moreover, our work from the 2D micropatterning system with clockwise cells such as human umbilical vein endothelial cell (HUVEC) lines (27) demonstrated that the activation of PKC signaling reverses chirality of endothelial cells from clockwise (CW) to CCW (35). Based on these results we identified PKC signaling as a promising candidate for regulating the chirality of cardiac cells.…”

Section: Resultsmentioning

confidence: 99%

“…One of the key findings of this study is that PKC activation reverses the handedness of cardiac looping and correspondingly the chirality of the cardiac cells. This is supported by the fact that PKC activators such as TPA and Indolactam V switch the chirality of endothelial cells from CW to CCW (35). One of the promising PKC isoform candidates is PKC-α which mediates the switch of cell chirality in endothelial cells.…”

Section: Discussionmentioning

confidence: 97%

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Intrinsic cellular chirality regulates left–right symmetry breaking during cardiac looping

Ray

Chin

Worley

et al. 2018

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

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The vertebrate body plan is overall symmetrical but left–right (LR) asymmetric in the shape and positioning of internal organs. Although several theories have been proposed, the biophysical mechanisms underlying LR asymmetry are still unclear, especially the role of cell chirality, the LR asymmetry at the cellular level, on organ asymmetry. Here with developing chicken embryos, we examine whether intrinsic cell chirality or handedness regulates cardiac C looping. Using a recently established biomaterial-based 3D culture platform, we demonstrate that chick cardiac cells before and during C looping are intrinsically chiral and exhibit dominant clockwise rotation in vitro. We further show that cells in the developing myocardium are chiral as evident by a rightward bias of cell alignment and a rightward polarization of the Golgi complex, correlating with the direction of cardiac tube rotation. In addition, there is an LR polarized distribution of N-cadherin and myosin II in the myocardium before the onset of cardiac looping. More interestingly, the reversal of cell chirality via activation of the protein kinase C signaling pathway reverses the directionality of cardiac looping, accompanied by a reversal in cellular biases on the cardiac tube. Our results suggest that myocardial cell chirality regulates cellular LR symmetry breaking in the heart tube and the resultant directionality of cardiac looping. Our study provides evidence of an intrinsic cellular chiral bias leading to LR symmetry breaking during directional tissue rotation in vertebrate development.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Intrinsic cellular chirality regulates left–right symmetry breaking during cardiac looping

Ray

Chin

Worley

et al. 2018

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

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“…The re‐positioning of tight junction proteins and proton pumps alters host cell absorption of ions and contributes to EPEC‐associated diarrhoea (Tapia, Kralicek, & Hecht, ). Furthermore, the importance of cell chirality, or cell asymmetry in the left‐to‐right axis, to endothelial permeability has also been recently demonstrated with regard to altered tight junction integrity during enteric infection (Fan et al, ). This is a novel finding as cell chirality was previously only associated with embryonic development (L. Q. Wan et al, ).…”

Section: The Physical Landscape and Ae Pathogensmentioning

confidence: 99%

Here, there, and everywhere: How pathogenicEscherichia colisense and respond to gastrointestinal biogeography

Woodward

Krekhno

2019

Cellular Microbiology

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Gastrointestinal (GI) pathogens enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC), and related mouse pathogen Citrobacter rodentium, are referred to as attaching and effacing (AE) pathogens for the lesions they form upon colonisation of the host epithelium. EPEC, EHEC, and C. rodentium are well known to use a type III secretion system to intimately attach to intestinal cells and secrete bacterial effectors to manipulate host cell processes. Less well known is the ability of AE pathogens to overcome significant physiological and microbial barriers and target specific gut niches for initial colonisation of the host epithelium. This review considers recent work highlighting the biogeography of the GI tract as it applies to colonisation by enteric pathogens, including environmental barriers to enteric infection, signals sensed by AE pathogens for navigation of the GI tract, and the tools AE pathogens use to respond to the changing host environment.

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“…[ 106 ] Rotational changes in stretch direction can induce reorientation of ECs to new axes, actin cytoskeletal reorganization, and changes in morphology. [ 107,108 ] Similar to shear stress, physiological CS (5–10%) helps maintain fundamental processes including angiogenic sprouting, matrix remodeling via MMP secretion, growth factor and vasomodulatory secretion, and protection from apoptosis via stretch‐activated ion channel stimulation, integrin engagement, and downstream mechanotransductive signaling. [ 42,109,110 ] However, pathological CS (>20%), caused by hypertension, can result in enhanced ROS and TNF‐α production, increased apoptosis, and imbalanced MMP secretion, ultimately affecting EC patency and permeability.…”

Section: Vascular Hemodynamics and Mechanotransductionmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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Cell chirality regulates intercellular junctions and endothelial permeability

Abstract: The handedness of the cell regulates the permeability of blood vessels.

Cited by 53 publications

References 50 publications

Intrinsic cellular chirality regulates left–right symmetry breaking during cardiac looping

Intrinsic cellular chirality regulates left–right symmetry breaking during cardiac looping

Here, there, and everywhere: How pathogenicEscherichia colisense and respond to gastrointestinal biogeography

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

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