Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Sapra, K. Tanuj; Medalia, Ohad

doi:10.3390/cells10081960

Cited by 19 publications

(11 citation statements)

References 155 publications

(218 reference statements)

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“…These protofilaments interact and cross each other frequently but seemingly without a strict pattern ( Figure 1d ). These sub-structures resembled the mammalian lamin filaments in shape and dimension [ 6 , 21 ]. The two filamentous structures often interacted with each other.…”

Section: Resultsmentioning

confidence: 99%

Filament assembly of the C. elegans lamin in the absence of helix 1A

Leeuw

Kronenberg-Tenga

Eibauer

et al. 2022

Nucleus

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Lamins are the major constituent of the nuclear lamina, a protein meshwork underlying the inner nuclear membrane. Nuclear lamins are type V intermediate filaments that assemble into ~3.5 nm thick filaments. To date, only the conditions for the in vitro assembly of Caenorhabditis elegans lamin ( Ce -lamin) are known. Here, we investigated the assembly of Ce -lamin filaments by cryo-electron microscopy and tomography. We show that Ce -lamin is composed of ~3.5 nm protofilaments that further interact in vitro and are often seen as 6–8 nm thick filaments. We show that the assembly of lamin filaments is undisturbed by the removal of flexible domains, that is, the intrinsically unstructured head and tail domains. In contrast, much of the coiled-coil domains are scaffold elements that are essential for filament assembly. Moreover, our results suggest that Ce -lamin helix 1A has a minor scaffolding role but is important to the lateral assembly regulation of lamin protofilaments.

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Section: Resultsmentioning

confidence: 99%

Filament assembly of the C. elegans lamin in the absence of helix 1A

Leeuw

Kronenberg-Tenga

Eibauer

et al. 2022

Nucleus

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“…Moreover, IFs have been shown to connect to the actin-associated cadherin and integrin adhesion receptors in a force-dependent manner [168]. Their abundance in the cytoplasm, physical robustness, and ability to strongly deform and stretch under force provide the cell with a powerful system to "buffer" and withstand mechanical stresses [169][170][171] and possibility counterbalance the focal-adhesion mediated forces [172].…”

Section: Intermediate Filamentsmentioning

confidence: 99%

Mechanotransduction in Skin Inflammation

Shutova

Boehncke

2022

Cells

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In the process of mechanotransduction, the cells in the body perceive and interpret mechanical stimuli to maintain tissue homeostasis and respond to the environmental changes. Increasing evidence points towards dysregulated mechanotransduction as a pathologically relevant factor in human diseases, including inflammatory conditions. Skin is the organ that constantly undergoes considerable mechanical stresses, and the ability of mechanical factors to provoke inflammatory processes in the skin has long been known, with the Koebner phenomenon being an example. However, the molecular mechanisms and key factors linking mechanotransduction and cutaneous inflammation remain understudied. In this review, we outline the key players in the tissue’s mechanical homeostasis, the available data, and the gaps in our current understanding of their aberrant regulation in chronic cutaneous inflammation. We mainly focus on psoriasis as one of the most studied skin inflammatory diseases; we also discuss mechanotransduction in the context of skin fibrosis as a result of chronic inflammation. Even though the role of mechanotransduction in inflammation of the simple epithelia of internal organs is being actively studied, we conclude that the mechanoregulation in the stratified epidermis of the skin requires more attention in future translational research.

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“…The mechanical properties of IFs are very different from those of actin filaments or microtubules (Sapra and Medalia, 2021;van Bodegraven and Etienne-Manneville, 2021). Single IFs are particularly flexible as shown by their short persistence length observed both in vitro and in cells.…”

Section: Structure and Mechanical Properties Of Intermediate Filamentsmentioning

confidence: 99%

“…Nuclear and cytoplasmic IFs are also highly stretchable. Depending on the experimental setting, desmin, vimentin, keratin or lamins IFs can be stretched by 240%-300% before breaking (Sapra and Medalia, 2021). IFs are not only very elastic; they also show a strain-stiffening response.…”

Section: Structure and Mechanical Properties Of Intermediate Filamentsmentioning

confidence: 99%

“…While the structural integrity of eukaryotic cells under small deformations involves actin filaments, microtubules, and IFs, the IF networks dominate the cytoplasmic mechanics and maintain cell viability under large deformations (Figure 1). Numerous studies probing intracellularly or extracellularly cell mechanical properties have shown that depletion of keratin, vimentin and desmin decreases cell stiffness [for a review, see (Sapra and Medalia, 2021;van Bodegraven and Etienne-Manneville, 2021)]. For instance, single cell nanomechanics experiments using AFM, magnetic and optical tweezers demonstrated that the deletion of type I or type II keratins decreases the Young's modulus of keratinocytes by more than 50% (Seltmann et al, 2013a;Ramms et al, 2013) (Table 1).…”

Section: Intermediate Filaments Contribution To Mechanics Of Migratin...mentioning

confidence: 99%

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Intermediate filaments: Integration of cell mechanical properties during migration

Infante

Etienne‐Manneville

2022

Front. Cell Dev. Biol.

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Cell migration is a vital and dynamic process required for the development of multicellular organisms and for immune system responses, tissue renewal and wound healing in adults. It also contributes to a variety of human diseases such as cancers, autoimmune diseases, chronic inflammation and fibrosis. The cytoskeleton, which includes actin microfilaments, microtubules, and intermediate filaments (IFs), is responsible for the maintenance of animal cell shape and structural integrity. Each cytoskeletal network contributes its unique properties to dynamic cell behaviour, such as cell polarization, membrane protrusion, cell adhesion and contraction. Hence, cell migration requires the dynamic orchestration of all cytoskeleton components. Among these, IFs have emerged as a molecular scaffold with unique mechanical features and a key player in the cell resilience to mechanical stresses during migration through complex 3D environment. Moreover, accumulating evidence illustrates the participation of IFs in signalling cascades and cytoskeletal crosstalk. Teaming up with actin and microtubules, IFs contribute to the active generation of forces required for cell adhesion and mesenchymal migration and invasion. Here we summarize and discuss how IFs integrate mechanical properties and signalling functions to control cell migration in a wide spectrum of physiological and pathological situations.

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Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Cited by 19 publications

References 155 publications

Filament assembly of the C. elegans lamin in the absence of helix 1A

Filament assembly of the C. elegans lamin in the absence of helix 1A

Mechanotransduction in Skin Inflammation

Intermediate filaments: Integration of cell mechanical properties during migration

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