Nucleoskeletal regulation of transcription: Actin on MRTF

Sidorenko, Ekaterina; Vartiainen, Maria K.

doi:10.1177/1535370219854669

Cited by 20 publications

(24 citation statements)

References 108 publications

(134 reference statements)

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“…Sidorenk and Vartiainen 38 review the important roles of actin, the nuclear lamina, and lamina binding proteins in regulation of transcription. The transcription complex MRTF-A/SRF is used as an example.…”

Section: Nucleoskeletal Proteinsmentioning

confidence: 99%

Cytoskeletal and nucleoskeletal interacting protein networks play critical roles in cellular function and dysfunction

Lambert

2019

Exp Biol Med (Maywood)

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Section: Nucleoskeletal Proteinsmentioning

confidence: 99%

Cytoskeletal and nucleoskeletal interacting protein networks play critical roles in cellular function and dysfunction

Lambert

2019

Exp Biol Med (Maywood)

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“…This would create a feedback loop, whereby reduced external tension on the cytoskeleton resulted in reduced pull on the nucleus, leading to downregulation of cytoskeletal and LINC components to “soften” the cell, which would then further reduce nuclear tension. It has been well established in recent years that the LINC complex plays a key role in regulating the transcriptomic response to mechanical stimuli [ 70 , 71 , 72 ]. Therefore, it is plausible that changes in LINC complex expression drive epidermal stratification and differentiation, rather than the LINC components altering in response to the differentiated phenotype observed in HEK cells on 4 kPa substrates.…”

Section: Discussionmentioning

confidence: 99%

Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro

Hunter-Featherstone

Young

Chamberlain

et al. 2021

Cells

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Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, which is significantly stiffer than the in vivo environment. Current epidermal models fail to consider the effects of culturing keratinocytes on plastic prior to setting up three-dimensional cultures, so the impact of this non-physiological exposure on epidermal assembly is largely overlooked. In this study, primary keratinocytes cultured on plastic were compared with those grown on 4, 8, and 50 kPa stiff biomimetic hydrogels that have similar mechanical properties to skin. Our data show that keratinocytes cultured on biomimetic hydrogels exhibited major changes in cellular architecture, cell density, nuclear biomechanics, and mechanoprotein expression, such as specific Linker of Nucleoskeleton and Cytoskeleton (LINC) complex constituents. Mechanical conditioning of keratinocytes on 50 kPa biomimetic hydrogels improved the thickness and organisation of 3D epidermal models. In summary, the current study demonstrates that the effects of extracellular mechanics on keratinocyte cell biology are significant and therefore should be harnessed in skin research to ensure the successful production of physiologically relevant skin models.

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“…Proteins that translocate to the cell nucleus through NPCs in response to mechanostimuli are mechanosensors if they react to cytoskeletal rearrangement when the ECM stiffens or their expression increases on rigid substrates ( Moreno-Vicente et al, 2018 ). They are mechanotransducers via their interaction with transcription factors in the cell nucleus, leading to changes in gene transcription ( Foster et al, 2017 ; Sidorenko and Vartiainen, 2019 ; Pocaterra and RomaniDupont, 2020 ). Here, mechanotransduction to the genes may be compared to delivery modes for which mechanical forces are converted into biochemical signals in the cytoplasm ( Figure 1A ).…”

Section: Evidence Of Mechanotransduction To the Genome In Cell Culturmentioning

confidence: 99%

3D Cell Culture for the Study of Microenvironment-Mediated Mechanostimuli to the Cell Nucleus: An Important Step for Cancer Research

Chhetri

Rispoli

Lelièvre

2021

Front. Mol. Biosci.

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The discovery that the stiffness of the tumor microenvironment (TME) changes during cancer progression motivated the development of cell culture involving extracellular mechanostimuli, with the intent of identifying mechanotransduction mechanisms that influence cell phenotypes. Collagen I is a main extracellular matrix (ECM) component used to study mechanotransduction in three-dimensional (3D) cell culture. There are also models with interstitial fluid stress that have been mostly focusing on the migration of invasive cells. We argue that a major step for the culture of tumors is to integrate increased ECM stiffness and fluid movement characteristic of the TME. Mechanotransduction is based on the principles of tensegrity and dynamic reciprocity, which requires measuring not only biochemical changes, but also physical changes in cytoplasmic and nuclear compartments. Most techniques available for cellular rheology were developed for a 2D, flat cell culture world, hence hampering studies requiring proper cellular architecture that, itself, depends on 3D tissue organization. New and adapted measuring techniques for 3D cell culture will be worthwhile to study the apparent increase in physical plasticity of cancer cells with disease progression. Finally, evidence of the physical heterogeneity of the TME, in terms of ECM composition and stiffness and of fluid flow, calls for the investigation of its impact on the cellular heterogeneity proposed to control tumor phenotypes. Reproducing, measuring and controlling TME heterogeneity should stimulate collaborative efforts between biologists and engineers. Studying cancers in well-tuned 3D cell culture platforms is paramount to bring mechanomedicine into the realm of oncology.

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Nucleoskeletal regulation of transcription: Actin on MRTF

Cited by 20 publications

References 108 publications

Cytoskeletal and nucleoskeletal interacting protein networks play critical roles in cellular function and dysfunction

Cytoskeletal and nucleoskeletal interacting protein networks play critical roles in cellular function and dysfunction

Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro

3D Cell Culture for the Study of Microenvironment-Mediated Mechanostimuli to the Cell Nucleus: An Important Step for Cancer Research

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