Skin under Strain: From Epithelial Model Tissues to Adult Epithelia

Püllen, Robin; Konrad, Jens; Merkel, Rudolf; Hoffmann, Bernd

doi:10.3390/cells10071834

Cited by 13 publications

(10 citation statements)

References 51 publications

(67 reference statements)

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“…A prediction of our current study is that increased changes in the force load affect desmosomal protein turnover. This hypothesis can be tested by controlled force application, e.g., in a tissue stretcher ( Faust et al, 2011 ; Pullen et al, 2021 ). A precedence for load-dependent bond formation and stabilization has been provided by analyses of E-cadherin ( Rakshit et al, 2012 ; Sivasankar, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Cortical tension regulates desmosomal morphogenesis

Moch

Schieren

Leube

2022

Front. Cell Dev. Biol.

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Mechanical stability is a fundamental and essential property of epithelial cell sheets. It is in large part determined by cell-cell adhesion sites that are tightly integrated by the cortical cytoskeleton. An intimate crosstalk between the adherens junction-associated contractile actomyosin system and the desmosome-anchored keratin intermediate filament system is decisive for dynamic regulation of epithelial mechanics. A major question in the field is whether and in which way mechanical stress affects junctional plasticity. This is especially true for the desmosome-keratin scaffold whose role in force-sensing is virtually unknown. To examine this question, we inactivated the actomyosin system in human keratinocytes (HaCaT) and canine kidney cells (MDCK) and monitored changes in desmosomal protein turnover.Partial inhibition of myosin II by para-nitro-blebbistatin led to a decrease of the cells' elastic modulus and to reduced desmosomal protein turnover in regions where nascent desmosomes are formed and, to a lower degree, in regions where larger, more mature desmosomes are present. Interestingly, desmosomal proteins are affected differently: a significant decrease in turnover was observed for the desmosomal plaque protein desmoplakin I (DspI), which links keratin filaments to the desmosomal core, and the transmembrane cadherin desmoglein 2 (Dsg2). On the other hand, the turnover of another type of desmosomal cadherin, desmocollin 2 (Dsc2), was not significantly altered under the tested conditions. Similarly, the turnover of the adherens junction-associated E-cadherin was not affected by the low doses of para-nitro-blebbistatin. Inhibition of actin polymerization by low dose latrunculin B treatment and of ROCK-driven actomyosin contractility by Y-27632 treatment also induced a significant decrease in desmosomal DspI turnover. Taken together, we conclude that changes in the cortical force balance affect desmosome formation and growth. Furthermore, they differentially modulate desmosomal protein turnover resulting in changes of desmosome composition. We take the observations as evidence for a hitherto unknown desmosomal mechanosensing and mechanoresponse pathway responding to an altered force balance.

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Section: Discussionmentioning

confidence: 99%

Cortical tension regulates desmosomal morphogenesis

Moch

Schieren

Leube

2022

Front. Cell Dev. Biol.

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“…To examine whether mammalian aPKCs regulate the mechanical resilience of multilayered stratified epithelia, e.g. the epidermis, we employed a micro-tissue stretcher 28 . In vitro stratified epidermal sheets (48 h differentiation in 1.8 mM high calcium medium) from primary control or aPKCλ −/− keratinocytes were subjected to external pulling forces while measuring the resisting force of the sheet until rupture 28 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Stratified keratinocyte sheets from 6 well plates were prepared as described for the sheet integrity assay. Keratinocyte sheets were then treated as described before 28 : sheets were transferred to a custom-made tissue stretcher, by placing them on a C-shaped PVDF-membrane frame, which served as carrier and distance piece. Together they were mounted in the holding frame.…”

Section: Methodsmentioning

confidence: 99%

Polarity signaling balances epithelial contractility and mechanical resistance

Rübsam

Püllen

Tellkamp

et al. 2023

Sci Rep

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Epithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt to and resist extrinsic mechanical forces enabled by keratin filament-linked desmosomes. How these two systems crosstalk to coordinate cellular movement and mechanical resilience is not known. Here we show that in stratifying epithelia the polarity protein aPKCλ controls the reorganization from stress fibers to cortical actomyosin during differentiation and upward movement of cells. Without aPKC, stress fibers are retained resulting in increased contractile prestress. This aberrant stress is counterbalanced by reorganization and bundling of keratins, thereby increasing mechanical resilience. Inhibiting contractility in aPKCλ−/− cells restores normal cortical keratin networks but also normalizes resilience. Consistently, increasing contractile stress is sufficient to induce keratin bundling and enhance resilience, mimicking aPKC loss. In conclusion, our data indicate that keratins sense the contractile stress state of stratified epithelia and balance increased contractility by mounting a protective response to maintain tissue integrity.

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“…Keratinocytes also provide a link to dermal tissue in association with the basement membrane. With aging, the epidermis becomes thinner and the healing of the epidermal barrier is impaired [14,15]. Even though keratinocytes are the main cell type in the epidermis, melanocytes, the cell producing pigment to protect people from ultraviolet radiation, are also located in the epidermis.…”

Section: The Mechanism Of Skin Agingmentioning

confidence: 99%

“…The dermis is composed of an extracellular matrix of collagenous, elastic fibers, and glycosaminoglycans, which are fibrillar proteins produced by the predominant cells, fibroblasts [13,15,16]. Besides fibroblasts, the dermis comprises dendritic cells, macrophages, mast cells, and other cells of the immune system.…”

Section: The Mechanism Of Skin Agingmentioning

confidence: 99%

Inflamm-Aging: A Mechanism of Aging That Contributes to the Characteristics of Skin Involvement in Systemic Sclerosis

Gökçen

2022

AAEE

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Aging is associated with deterioration of the immune function. Two contributory mechanisms are inflamm-aging, which is a chronic, low-grade systemic inflammation, and immunosenescence, an impairment of adaptive immune function that may also contribute to the development of inflamm-aging. This age-related inflammatory event is associated with alteration to the balance of pro-inflammatory and anti-inflammatory cytokines. The effect of inflamm-aging on skin aging in healthy people is accepted; however, its effect on normal skin aging and/or skin characteristics in systemic sclerosis is unknown. The hypothesis presented herein suggests that inflamm-aging may contribute to the evolution of the skin phases in systemic sclerosis, which progress from edematous, fibrotic, and indurative phases to the atrophic phase.

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Skin under Strain: From Epithelial Model Tissues to Adult Epithelia

Cited by 13 publications

References 51 publications

Cortical tension regulates desmosomal morphogenesis

Cortical tension regulates desmosomal morphogenesis

Polarity signaling balances epithelial contractility and mechanical resistance

Inflamm-Aging: A Mechanism of Aging That Contributes to the Characteristics of Skin Involvement in Systemic Sclerosis

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