Probing compression versus stretch activated recruitment of cortical actin and apical junction proteins using mechanical stimulations of suspended doublets

Gao, Xumei; Acharya, Bipul R.; Engl, Wilfried; Mets, Richard De; Thiery, Jean Paul; Yap, Alpha; Viasnoff, Virgile

doi:10.1063/1.5025216

Cited by 15 publications

(20 citation statements)

References 37 publications

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“…Junctional tension, like that produced by actomyosin forces, recruits the TJ components ZO1 and occludin to promote barrier function in simple polarized epithelia [47, 49]. Dsg1 loss perturbed the normally restricted pattern of vinculin in the high-tension layer where TJs form, consistent with the idea that higher tension cell-cell junctions occurred in the lower layers (Figure 4A).…”

Section: Discussionsupporting

confidence: 64%

“…In multiple models, TJs and their protein components have been suggested to be sensitive to mechanical input [2, 47–49]. We hypothesize the patterning of the desmosome/IF components drives polarized, layer-specific epidermal functions; thus we next assessed the effects of uncoupling the desmosome/IF linkage on the ensuing development of the epidermal TJ barrier.…”

Section: Resultsmentioning

confidence: 99%

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Desmosomes polarize mechanical signaling to govern epidermal tissue form and function

Broussard¹,

Koetsier²,

Hegazy³

et al. 2020

Preprint

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The epidermis is a stratified epithelium in which structural and functional features are polarized across multiple cell layers. This type of polarity is essential for establishing the epidermal barrier, but how it is created and sustained is poorly understood. Previous work identified a role for the classical cadherin/filamentous-actin network in establishment of epidermal polarity. However, little is known about potential roles of the most prominent epidermal intercellular junction, the desmosome, in establishing epidermal polarity, in spite of the fact that desmosome constituents are patterned across the apical to basal cell layers. Here, we show that desmosomes and their associated intermediate filaments (IF) are key regulators of mechanical polarization in epidermis, whereby basal and suprabasal cells experience different forces that drive layer-specific functions. Uncoupling desmosomes and IF or specific targeting of apical desmosomes through depletion of the superficial desmosomal cadherin, desmoglein 1, impedes basal (stratification) and suprabasal (tight junction barrier) functions. Surprisingly, disengaging desmosomes from IF also uncouples stratification from differentiation, accelerating the expression of differentiation markers. Our data support a model in which the desmosome-IF network supports a reciprocally organized distribution of ErbB1/EGFR activity in the basal layer and mechanosensitive kinase ErbB2 activity in the suprabasal layer to ensure the proper spatiotemporal coordination of cell mechanics and the biochemical program of differentiation.

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Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Desmosomes polarize mechanical signaling to govern epidermal tissue form and function

Broussard¹,

Koetsier²,

Hegazy³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In multiple models, TJs and their protein components have been suggested to be mechanosensitive. 2,[47][48][49] We hypothesize the patterning of the desmosome/IF components drives polarized, layer-specific epidermal functions. Thus, we assessed the effects DPNTP expression on epidermal TJ barrier development.…”

Section: Uncoupling the Desmosome/if Connection Diminishes Epidermal Keratinocyte Barrier Functionmentioning

confidence: 99%

Desmosomes polarize and integrate chemical and mechanical signaling to govern epidermal tissue form and function

et al. 2021

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“…2 C) to test our hypothesis. We test our model hypothesis against previous experimental observations of ecadherin and actin dynamics in S180 cell doublets [28,29]. In these experiments, two S180 cells were suspended within a microfluidic device and e-cadherin and actin distributions at the contact rim were observed.…”

Section: Coupling the Lattice-based Model With The Reaction-diffusionmentioning

confidence: 84%

“…However, if the actin filament polymerization and stabilization drug, Jasplakinolide (Jasp), is applied to the cell doublet before the introduction of flow, the asymmetric distribution of the E-cadherin disappears when stress is applied to one side of the contact rim in the experimental study [29]. To simulate the effect of the Jasp, we introduced an additional actin polymerization term in the RD model and set the kinetic constant k0 to be a large value, which turns most actin monomers into F-actin.…”

Section: Resultsmentioning

confidence: 99%

Cortical Tension Initiates the Positive Feedback Loop Between E-cadherin and F-actin

Holmes

Thiery

et al. 2021

Preprint

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Adherens junctions (AJs) physically link two cells at their contact interface via extracellular homophilic interactions between cadherin molecules and intracellular connections between cadherins and the actomyosin cortex. Both cadherin and actomyosin cytoskeletal dynamics are reciprocally regulated by mechanical and chemical signals, which subsequently determine the strength of cell-cell adhesions and the emergent organization and stiffness of the tissues they form. However, an understanding of the integrated system is lacking. We present a new mechanistic computational model of intercellular junction maturation in a cell doublet to investigate the mechano-chemical crosstalk that regulates AJ formation and homeostasis. The model couples a 2D lattice-based model of cadherin dynamics with a continuum, reaction-diffusion model of the reorganizing actomyosin network through its regulation by Rho signaling at the intercellular junction. We demonstrate that local immobilization of cadherin induces cluster formation in a cis less dependent manner. We further investigate how cadherin and actin regulate and cooperate. By considering the force balance during AJ maturation and the force-sensitive property of the cadherin/F-actin linking molecules, we show that cortical tension applied on the contact rim can explain the ring distribution of cadherin and F-actin on the cell-cell contact of the cell-doublet. Meanwhile, the positive feedback loop between cadherin and F-actin is necessary for maintenance of the ring. Different patterns of cadherin distribution can be observed as an emergent property of disturbances of this feedback loop. We discuss these findings in light of available experimental observations on underlying mechanisms related to cadherin/F-actin binding and the mechanical environment.

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Probing compression versus stretch activated recruitment of cortical actin and apical junction proteins using mechanical stimulations of suspended doublets

Cited by 15 publications

References 37 publications

Desmosomes polarize mechanical signaling to govern epidermal tissue form and function

Desmosomes polarize mechanical signaling to govern epidermal tissue form and function

Desmosomes polarize and integrate chemical and mechanical signaling to govern epidermal tissue form and function

Cortical Tension Initiates the Positive Feedback Loop Between E-cadherin and F-actin

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