Biomaterial-based mechanical regulation facilitates scarless wound healing with functional skin appendage regeneration

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Фев. 18, 2024

Abstract Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss appendages, ultimately impairing its normal physiological function. Accumulating evidence underscores potential targeted modulation mechanical cues enhance regeneration, promoting scarless repair by influencing extracellular microenvironment driving phenotypic transitions. The field appendage regeneration has witnessed remarkable advancements in utilization biomaterials with distinct physical properties. However, a comprehensive understanding underlying mechanisms remains somewhat elusive, limiting broader application these innovations. In this review, we present two promising biomaterial-based approaches aimed at bolstering regenerative capacity compromised skin. first approach involves leveraging specific biophysical properties create an optimal environment that supports cellular activities essential for regeneration. second centers on harnessing forces exerted plasticity, facilitating efficient reprogramming and, consequently, appendages. summary, manipulation using strategies holds significant promise as supplementary achieving wound healing, coupled restoration multiple functions.

Язык: Английский

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Cytoskeletal crosstalk: A focus on intermediate filaments

Current Opinion in Cell Biology, Год журнала: 2024, Номер 87, С. 102325 - 102325

Опубликована: Фев. 14, 2024

The cytoskeleton, comprising actin microfilaments, microtubules, and intermediate filaments, is crucial for cell motility tissue integrity. While prior studies largely focused on individual cytoskeletal networks, recent research underscores the interconnected nature of these systems in fundamental cellular functions like adhesion, migration, division. Understanding coordination distinct networks both time space essential. This review synthesizes current findings intricate interplay between emphasizing pivotal role filaments. Notably, filaments engage extensive crosstalk with microfilaments microtubules through direct molecular interactions, linkers, motors that form bridges, as well via more complex regulation intracellular signaling.

Язык: Английский

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From Cell Architecture to Mitochondrial Signaling: Role of Intermediate Filaments in Health, Aging, and Disease

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1100 - 1100

Опубликована: Янв. 27, 2025

The coordination of cytoskeletal proteins shapes cell architectures and functions. Age-related changes in cellular mechanical properties have been linked to decreased tissue dysfunction. Studies also found a relationship between mitochondrial function the cytoskeleton. Cytoskeleton inhibitors impact quality function, including motility morphology, membrane potential, respiration. regulatory cytoskeleton on functions are involved pathogenesis several diseases. Disassembly axon’s release neurofilament fragments documented during neurodegeneration. However, these can be related impairments, spanning from reduced altered bioenergetics. Herein, we discuss recent research highlighting some pathophysiological roles disassembly aging, neurodegeneration, neuromuscular diseases, with focus studies that explored intermediate filaments signaling as relevant contributors health disease.

Язык: Английский

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Nonaffine Mechanics of Entangled Networks Inspired by Intermediate Filaments

Physical Review Letters, Год журнала: 2023, Номер 131(5)

Опубликована: Авг. 4, 2023

Inspired by massive intermediate filament (IF) reorganization in superstretched epithelia, we examine computationally the principles controlling mechanics of a set entangled filaments whose ends slide on cell boundary. We identify an entanglement metric and threshold beyond which random loose networks respond nonaffinely nonlinearly to stretch self-organizing into structurally optimal star-shaped configurations. A simple model connecting cellular strains links emergent geometry, network topology, mechanics. safety net mechanism IF provide framework harness soft fibrous materials.

Язык: Английский

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Arp2/3 complex activity enables nuclear YAP for naïve pluripotency of human embryonic stem cells

eLife, Год журнала: 2024, Номер 13

Опубликована: Сен. 25, 2024

Our understanding of the transitions human embryonic stem cells (hESCs) between distinct stages pluripotency relies predominantly on regulation by transcriptional and epigenetic programs with limited insight role established morphological changes. We report remodeling actin cytoskeleton hESCs as they transition from primed to naïve which includes assembly a ring contractile filaments encapsulating colonies hESCs. Activity Arp2/3 complex is required for formation ring, establish uniform cell mechanics within colonies, promote nuclear translocation Hippo pathway effectors YAP TAZ, effective pluripotency. RNA-sequencing analysis confirms that activity regulates signaling in hESCs, impaired inhibited rescued expressing constitutively active, nuclear-localized YAP-S127A. Moreover, expression YAP-S127A partially restores filament fence inhibition, suggesting both upstream downstream activity. These new findings biology reveal mechanism cytoskeletal dynamics coordinating regulate gene facilitate states.

Язык: Английский

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The redox-responsive roles of intermediate filaments in cellular stress detection, integration and mitigation

Current Opinion in Cell Biology, Год журнала: 2023, Номер 86, С. 102283 - 102283

Опубликована: Ноя. 20, 2023

Intermediate filaments are critical for cell and tissue homeostasis stress responses. Cytoplasmic intermediate form versatile dynamic assemblies that interconnect cellular organelles, participate in signaling protect cells tissues against stress. Here we have focused on their involvement redox oxidative stress, which arises numerous pathophysiological situations. We pay special attention to type III filaments, mainly vimentin, because it provides a physical interface signaling, responses mechanosensing. Vimentin possesses single cysteine residue is target multiple oxidants electrophiles. This conserved fine tunes vimentin assembly, response crosstalk with other structures. integrate evidence from the filament biology fields propose as sentinel networks of cell. To support this, appraise how detects orchestrates electrophilic

Язык: Английский

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Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin

Communications Materials, Год журнала: 2024, Номер 5(1)

Опубликована: Янв. 15, 2024

Abstract The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering mechanoresponses. However, it has been unclear if stiffness-dependent is induced solely by myosin activity. Here, we report that in absence contractility, 3T3 fibroblasts still transmit levels traction. This myosin-independent traction regulated polymerizing actin assisted nucleators Arp2/3 and formin where a stronger contribution than to both flow. Intriguingly, despite only slight changes F-actin flow speed observed cells with combined inhibition compared sole inhibition, they show 4-times reduction myosin-only inhibition. Our analyses indicate traditional models based on rigid are inadequate for capturing such dramatic force similar Instead, incorporating network’s viscoelastic properties crucial. new model including viscoelasticity reveals enhance sensitivity mechanically reinforcing network, thereby facilitating more effective transmission flow-induced forces. validated cell measurement atomic microscopy experimental observation model-predicted fluctuation.

Язык: Английский

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The Role of Vimentin in Human Corneal Fibroblast Spreading and Myofibroblast Transformation

Cells, Год журнала: 2024, Номер 13(13), С. 1094 - 1094

Опубликована: Июнь 25, 2024

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, cell-matrix adhesion, and fibrotic transformation. Here, we assess how vimentin impacts morphology, myofibroblast transformation of human corneal fibroblasts. Overall, although knockout (KO) did not dramatically impact fibroblast spreading mechanical activity (traction force), elongation response PDGF was reduced KO cells compared controls. Blocking polymerization using Withaferin had even more pronounced effects on also inhibited cell-induced matrix contraction. Furthermore, absence completely block TGFβ-induced transformation, the degree amount αSMA protein expression reduced. Proteomics showed that cultured TGFβ a similar pattern One exception included periostin, an ECM associated with wound healing fibrosis other types, which highly expressed only Vim cells. We demonstrate for first time LRRC15, previously cancer-associated fibroblasts, is by myofibroblasts. Interestingly, proteins LRRC15 collagen, fibronectin, β1 integrin α11 integrin, were upregulated. our data show both identified novel may regulate presence and/or vimentin.

Язык: Английский

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RhoA/ROCK-TAZ Axis regulates bone formation within calvarial trans-sutural distraction osteogenesis

Cellular Signalling, Год журнала: 2024, Номер 121, С. 111300 - 111300

Опубликована: Июль 14, 2024

Craniofacial skeletal deformities can be addressed by applying tensile force to sutures prompt sutural bone formation. The intricate process of mechanical modulation in craniofacial involves complex biomechanical signal transduction. small GTPase Ras homolog gene family member A (RhoA) functions as a key mechanotransduction protein, orchestrating the dynamic assembly cytoskeleton activating Rho-associated coiled-coil containing protein kinase (ROCK). Transcriptional coactivator with PDZ-binding motif (TAZ) serves crucial mediator regulation genes and orchestration biological within signaling pathway. However, role RhoA/ROCK-TAZ trans-sutural distraction osteogenesis has not been reported.

Язык: Английский

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Intermediate filaments at a glance

Journal of Cell Science, Год журнала: 2024, Номер 137(16)

Опубликована: Авг. 15, 2024

Intermediate filaments (IFs) comprise a large family of versatile cytoskeletal proteins, divided into six subtypes with tissue-specific expression patterns. IFs have wide repertoire cellular functions, including providing structural support to cells, as well active roles in mechanical and signaling pathways. Consequently, defects are associated more than 100 diseases. In this Cell Science at Glance article, we discuss the established classes their general features, functions beyond support, recent advances field. We also highlight involvement disease potential use clinical markers pathological conditions. Finally, provide our view on current knowledge gaps future directions IF

Язык: Английский

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