Cellular mechanics of wound formation in single cell layer under cyclic stretching

Xu, Jiayi; Xu, Xiangyu; Li, Xiaojun; He, Shijie; Li, Dechang; Ji, Baohua

doi:10.1016/j.bpj.2021.12.015

Cited by 21 publications

(8 citation statements)

References 39 publications

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“…Instead, we observed that the cells which were parallel to the direction of stretch maintained their elongation, and cells that were perpendicular to the direction of stretch retracted and/or reoriented away from the stretch direction. Cyclically stretched epithelial (MDCK) cells have been shown to increase their polarization (aspect ratio) when aligned around a "wound" edge in a monolayer model with a hole (essentially the inverse of our "island" system) consistent with the behavior we observe for cells aligned with the stretch axis, but the retraction of edge cells perpendicular to stretch has not been reported (Xu et al 2022). It is possible that the aligned bands in our system disrupt the emergent radial-symmetric stress field resulting in relatively low stress in edge cells, thus these cells reorient in the stretch direction to increase their stress towards a homeostatic level or to minimize shear stress (Liu et al 2016).…”

Section: Discussionsupporting

confidence: 82%

Multicellular Aligned Bands Disrupt Global Collective Cell Behavior

Jebeli

Lopez

Goldblatt

et al. 2022

Preprint

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Mechanical stress patterns emerging from collective cell behavior have been shown to play critical roles in morphogenesis, tissue repair, and cancer metastasis. In our previous work utilizing microcontact printing to geometrically constrain valvular interstitial cell monolayers into specific shapes, we demonstrated that the general patterns of observed cell alignment, size, and apoptosis correlate with predicted mechanical stress fields if nonuniform cell properties are used in the computational models. However, these radially symmetric models did not predict the substantial heterogeneity in cell behavior observed in individual circular aggregates. The goal of this study is to determine how the heterogeneities in cell behavior emerge over time and diverge from the predicted collective cell behavior. Cell-cell interactions in circular multicellular aggregates of valvular interstitial cells were studied with time-lapse imaging ranging from hours to days, and migration, proliferation, and traction stresses were measured. Our results indicate that individual elongated cells create strong local alignment within pre-confluent cell populations on the microcontact printed protein islands. These cells influence the alignment of additional cells to create dense, locally aligned bands of cells which disrupt the global behavior. Cells are highly elongated at the endpoints of the bands yet have decreased spread area in the middle and reduced mobility. Although traction stresses at the endpoints of bands are enhanced, even to the point of detaching aggregates from the culture surface, the cells in dense bands exhibit reduced proliferation, less nuclear YAP, and increased apoptotic rates indicating a low stress environment. These findings suggest that strong local cell-cell interactions between primary fibroblastic cells can disrupt the global collective cellular behavior leading to substantial heterogeneity of cell behaviors in constrained monolayers. This local emergent behavior within aggregated fibroblasts may play an important role in development and disease of connective tissues.

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Section: Discussionsupporting

confidence: 82%

Multicellular Aligned Bands Disrupt Global Collective Cell Behavior

Jebeli

Lopez

Goldblatt

et al. 2022

Preprint

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“…Though viability across different time points has been previously reported in indirect tests for CPs, 50 to our knowledge there has been no work reported on viability based on different cell seeding densities. In this work, investigating viability on both high-density and low-density cells was considered critical to cover the scenarios for sampling in healthy skin (high cell density representing intact skin) and damaged skin (where the cells may be less dense), 51 particularly as cell density is one of the important parameters in cell culture as it can impact the cell's rate of differentiation or viability in response to cytotoxicity. 52 4.1.…”

Section: Resultsmentioning

confidence: 99%

Cell Viability Assessment of PEDOT Conducting Polymer-Coated Microneedles for Skin Sampling

Mokhtar,

Derrick-Roberts,

Evans

et al. 2023

ACS Appl. Bio Mater.

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Recently, transdermal monitoring and drug delivery have gained much interest, owing to the introduction of the minimally invasive microneedle (MN) device. The advancement of electroactive MNs electrically assisted in the capture of biomarkers or the triggering of drug release. Recent works have combined conducting polymers (CPs) onto MNs owing to the soft nature of the polymers and their tunable ionic and electronic conductivity. Though CPs are reported to work safely in the body, their biocompatibility in the skin has been insufficiently investigated. Furthermore, during electrical biasing of CPs, they undergo reduction or oxidation, which in practical terms leads to release/exchange of ions, which could pose biological risks. This work investigates the viability and proliferation of skin cells upon exposure to an electrochemically biased MN pair comprising two differently doped poly(3,4-ethylenedioxy-thiophene) (PEDOT) polymers that have been designed for skin sampling use. The impact of biasing on human keratinocytes and dermal fibroblasts was determined at different initial cell seeding densities and incubation periods. Indirect testing was employed, whereby the culture media was first exposed to PEDOTs prior to the addition of this extract to cells. In all conditions, both unbiased and biased PEDOT extracts showed no cytotoxicity, but the viability and proliferation of cells cultured at a low cell seeding density were lower than those of the control after 48 h of incubation.

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“…We have shown that epithelial–cancerous monolayer interaction can induce evident alterations in cytoskeleton arrangement, cell shapes, actomyosin contractility, cell extrusion, and cell apoptosis near the interface. These self-adaptive behaviors at the subcellular and cellular scales may generally affect the mechanical properties, fluid–solid transition, rheology, and rigidity of epithelial tissues. ,,− It has been shown that the mechanical properties of paracancerous tissues play an essential role in suppressing tumor progression . For example, enhanced stiffness of host tissues can inhibit tumor expansion .…”

Section: Discussionmentioning

confidence: 99%

Interfacial Organization and Forces Arising from Epithelial–Cancerous Monolayer Interactions

Guan,

Lin,

Chen

et al. 2023

ACS Nano

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Cellular mechanics of wound formation in single cell layer under cyclic stretching

Cited by 21 publications

References 39 publications

Multicellular Aligned Bands Disrupt Global Collective Cell Behavior

Multicellular Aligned Bands Disrupt Global Collective Cell Behavior

Cell Viability Assessment of PEDOT Conducting Polymer-Coated Microneedles for Skin Sampling

Interfacial Organization and Forces Arising from Epithelial–Cancerous Monolayer Interactions

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