Appreciating the role of cell shape changes in the mechanobiology of epithelial tissues DOI Creative Commons
Marine Luciano, Marie Versaevel, Eléonore Vercruysse

et al.

Biophysics Reviews, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 1, 2022

The wide range of epithelial cell shapes reveals the complexity and diversity intracellular mechanisms that serve to construct their morphology regulate functions. Using mechanosensitive steps, cells can sense a variety different mechanochemical stimuli adapt behavior by reshaping morphology. These changes shape rely on structural reorganization in space time generates modifications tensional state activates biochemical cascades. Recent studies have started unveil how maintenance is involved mechanical homeostatic tasks sustain tissue folding, identity, self-renewal. Here, we review relevant works integrated mechanobiology elucidate some core principles may be conveyed into spatial information guide collective processes such as morphogenesis. Among many other parameters, show regulation understood result interplay between two counteracting mechanisms: actomyosin contractility intercellular adhesions, both do not act independently but are functionally operate molecular, cellular, scales. We highlight role cadherin-based adhesions force-sensing mechanotransduction, report recent developments exploit physics liquid crystals connect orientational order aggregates. Finally, emphasize further intermingling disciplines develop new assays will lead way toward unified picture contribution pathophysiological tissues.

Language: Английский

Permeability of the Endothelial Barrier: Identifying and Reconciling Controversies DOI Creative Commons
Lena Claesson‐Welsh, Elisabetta Dejana, Donald M. McDonald

et al.

Trends in Molecular Medicine, Journal Year: 2020, Volume and Issue: 27(4), P. 314 - 331

Published: Dec. 11, 2020

In the microcirculation, endothelial permeability varies from least in arterioles to greatest venules and is regulated an organ-specific manner control extravasation of fluid, solutes, large molecules.Inflammatory factors increase vascular by inducing formation focal gaps that can be transient acute inflammation or sustained chronic conditions.Gap requires changes organization tight junctions adherens join cells create a barrier.Adherens junction opening phosphorylation, loss homophilic interactions, internalization VE-cadherin accompanied cortical cytoskeleton.Sustained hyperpermeability pathologic conditions lead edema, reduced perfusion, impaired drug delivery, exaggerated disease severity. Leakage blood vessels into tissues governed mechanisms barrier function maintain homeostasis. Dysregulated contributes many influence morbidity treatment. Diverse approaches used study have yielded wealth valuable insights. Yet, ongoing questions, technical challenges, unresolved controversies relating relative contributions regulation, transendothelial sieving, transport particulates complicate interpretations context physiology pathophysiology. Here, we describe recent vivo findings other advances understanding with goal identifying reconciling over cellular molecular processes regulate health disease.

Language: Английский

Citations

443
High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows DOI Creative Commons

Hesham Azizgolshani,

Jonathan Coppeta,

Else M. Vedula

et al.

Lab on a Chip, Journal Year: 2021, Volume and Issue: 21(8), P. 1454 - 1474

Published: Jan. 1, 2021

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue vitro, therefore providing route model. However, OOC technologies are often created at the expense throughput, industry-standard form factors, compatibility with state-of-the-art data collection tools. Here we present an platform supporting variety human models including liver, vascular, gastrointestinal, kidney. The has 96 devices per industry standard plate contemporary high-throughput Specifically, demonstrate programmable flow control over two relevant regimes: perfusion that enhances hepatic function high-shear stress aligns endothelial monolayers. In addition, integrate electrical sensors, demonstrating quantification barrier primary gut colon real-time. We utilize optical access tissues directly quantify renal active transport oxygen consumption via integrated sensors. Finally, leverage throughput screen all using high content screening (HCS) evaluate gene expression RNA sequencing (RNA-seq). By combining these one platform, physiologically-relevant can be generated measured, accelerating optimization model, ultimately increasing accuracy drug screening.

Language: Английский

Citations

160
Patterning of the cell cortex by Rho GTPases DOI
William M. Bement, Andrew B. Goryachev, Ann L. Miller

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(4), P. 290 - 308

Published: Jan. 3, 2024

Language: Английский

Citations

50
A short guide to the tight junction DOI Creative Commons
Sandra Citi, Michael Fromm, Mikio Furuse

et al.

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(9)

Published: May 1, 2024

ABSTRACT Tight junctions (TJs) are specialized regions of contact between cells epithelial and endothelial tissues that form selective semipermeable paracellular barriers establish maintain body compartments with different fluid compositions. As such, the formation TJs represents a critical step in metazoan evolution, allowing multicompartmental organisms true, barrier-forming epithelia endothelia. In six decades have passed since first observations by transmission electron microscopy, much progress has been made understanding structure, function, molecular composition regulation TJs. The goal this Perspective is to highlight key concepts emerged through research future challenges lie ahead for field.

Language: Английский

Citations

29
Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function DOI Creative Commons

Fernanda Schreiber,

Iulia Balas,

Matthew J. Robinson

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 477 - 477

Published: March 8, 2024

The gut mucosal epithelium is one of the largest organs in body and plays a critical role regulating crosstalk between resident microbiome host. To this effect, tight control what permitted through barrier high importance. There should be restricted passage harmful microorganisms antigens while at same time allowing absorption nutrients water. An increased permeability, or “leaky gut”, has been associated with variety diseases ranging from infections, metabolic diseases, inflammatory autoimmune to neurological conditions. Several factors can affect including cytokines, dietary components, microbiome. Here, we discuss how impacts permeability epithelial harnessed for therapeutic purposes.

Language: Английский

Citations

23
Molecular architecture and assembly of the tight junction backbone DOI
Jörg Piontek, Susanne M. Krug, Jonas Protze

et al.

Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Year: 2020, Volume and Issue: 1862(7), P. 183279 - 183279

Published: March 26, 2020

Language: Английский

Citations

93
Scaffolding proteins of vertebrate apical junctions: structure, functions and biophysics DOI Creative Commons

Florian Rouaud,

Sophie Sluysmans, Arielle Flinois

et al.

Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Year: 2020, Volume and Issue: 1862(10), P. 183399 - 183399

Published: June 16, 2020

Tight and adherens junctions are specialized sites of cell-cell interaction in epithelia endothelia, involved barrier, adhesion, signaling functions. These functions orchestrated by a highly organized meshwork macromolecules the membrane cytoplasmic compartments. In this review, we discuss structural organization major scaffolding adaptor proteins vertebrate apical (ZO proteins, afadin, PLEKHA7, cingulin, paracingulin, polarity complex few others), focusing on their interactions with cytoskeletal proteins. Furthermore, recent results highlighting how mechanical tension, protein-protein post-translational modifications regulate conformation function spontaneous phase separation into biomolecular condensates contributes to junction assembly. Using sequence-based algorithm, large fraction predicted be separating (PSPs), suggesting that formation is general mechanism organize contacts clustering

Language: Английский

Citations

81
Interplay between Extracellular Matrix Stiffness and JAM-A Regulates Mechanical Load on ZO-1 and Tight Junction Assembly DOI Creative Commons
Alexis J. Haas, Ceniz Zihni, Artur Ruppel

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 32(3), P. 107924 - 107924

Published: July 1, 2020

Tight-junction-regulated actomyosin activity determines epithelial and endothelial tension on adherens junctions drives morphogenetic processes; however, whether or not tight themselves are under tensile stress is clear. Here, we use a sensor based ZO-1, scaffolding protein that links the junctional membrane to cytoskeleton, determine if carry mechanical load. Our data indicate ZO-1 forces acting regulated by extracellular matrix (ECM) stiffness adhesion molecule JAM-A. JAM-A depletion stimulates recruitment of p114RhoGEF/ARHGEF18, traction at focal adhesions. p114RhoGEF required for activation junction integrity stiff but soft ECM. Thus, bears load, assembly interplay between physical properties ECM adhesion-regulated signaling junctions.

Language: Английский

Citations

73
Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling DOI Creative Commons
Saranyaraajan Varadarajan, Shahana Chumki, Rachel E. Stephenson

et al.

The Journal of Cell Biology, Journal Year: 2022, Volume and Issue: 221(4)

Published: March 7, 2022

Epithelial cell–cell junctions remodel in response to mechanical stimuli maintain barrier function. Previously, we found that local leaks tight (TJs) are rapidly repaired by local, transient RhoA activation, termed “Rho flares,” but how Rho flares regulated is unknown. Here, discovered intracellular calcium flashes and junction elongation early events the flare pathway. Both laser-induced naturally occurring TJ breaks lead at site of leaks. Additionally, induced optogenetics increases frequency, suggesting mechanically triggered. Depletion or inhibition mechanosensitive channels (MSCs) reduces amplitude diminishes sustained activation flares. MSC-dependent influx necessary global function regulating reinforcement proteins via contraction. In all, uncovered a novel role for remodeling, allowing epithelial cells repair stimuli.

Language: Английский

Citations

57
Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids? DOI Creative Commons
Susana Lechuga, Manuel B. Braga Neto, Nayden G. Naydenov

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 16, 2023

Disruption of the intestinal epithelial barrier is a hallmark mucosal inflammation. It increases exposure immune system to luminal microbes, triggering perpetuating inflammatory response. For several decades, stimuli-induced breakdown human gut was studied in vitro by using colon cancer derived cell lines. While providing wealth important data, these lines do not completely mimic morphology and function normal cells (IEC) due cancer-related chromosomal abnormalities oncogenic mutations. The development organoids provided physiologically-relevant experimental platform study homeostatic regulation disease-dependent dysfunctions barrier. There need align integrate emerging data obtained with classical studies that utilized This review discusses utilization dissect roles mechanisms disruption during We summarize available generated two major types from either crypts or induced pluripotent stem compare them results earlier conventional identify research areas where complementary use cancer-derived advance our understanding inflamed unique questions could be addressed only organoid platforms.

Language: Английский

Citations

34