Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back

Ndiaye, Anne-Betty; Koenderink, Gijsje H.; Shemesh, Mordechai

doi:10.3389/fcell.2022.882037

Cited by 20 publications

(9 citation statements)

References 123 publications

(128 reference statements)

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“…Adaptation of the morphological and mechanical state of a cell occurs at a timescale of seconds to hours [73][74][75][76][77] , which is in line with the observation that vimentin-expressing cells have reached a homeostatic state after 24 h. However, vimentin-depleted cells reach mechanical homeostasis only after 48 h, therefore, pointing towards the existence of a compensation mechanism that occurs in a timespan of days. It is worth noting that production and remodeling of ECM is a process occurring at longer timescales.…”

Section: Discussionsupporting

confidence: 80%

Environmental stiffness restores mechanical homeostasis in vimentin-depleted cells

Grolleman,

Engeland,

Raza

et al. 2023

Preprint

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Recent experimental evidence indicates a role for the intermediate filament vimentin in regulating cellular mechanical homeostasis, but its precise contribution remains to be discovered. Mechanical homeostasis requires a balanced bi-directional interplay between the cell its microenvironment and the cellular morphological and mechanical state, this balance being regulated via processes of mechanotransduction and mechanoresponse, commonly referred to as mechanoreciprocity. Here, we systematically analyze vimentin-expressing and vimentin-depleted cells in a swatch of in vitro cellular microenvironments varying in stiffness and/or ECM density. We find that vimentin-expressing cells maintain mechanical homeostasis by adapting cellular morphology and mechanics to micromechanical changes in the microenvironment. However, vimentin-depleted cells lose this mechanoresponse ability on short timescales, only to reacquire it on longer time scales. Indeed, we find that the morphology and mechanics of vimentin-depleted cell in stiffened microenvironmental conditions can get restored to the homeostatic levels of vimentin-expressing cells. Additionally, we observed vimentin-depleted cells increasing collagen matrix synthesis and its crosslinking, a phenomenon which is known to increase matrix stiffness, and which we now hypothesize to be a cellular compensation mechanism for the loss of vimentin. Taken together, our findings provide further insight in the regulating role of intermediate filament vimentin in mediating mechanoreciprocity and mechanical homeostasis.

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Section: Discussionsupporting

confidence: 80%

Environmental stiffness restores mechanical homeostasis in vimentin-depleted cells

Grolleman,

Engeland,

Raza

et al. 2023

Preprint

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“…The intermediate filament protein vimentin plays key roles in cell architecture and mechanotransduction [1][2][3]. Nevertheless, at least equally important are its roles in the integration of cellular structures and signaling pathways, with consequences on organelle homeostasis, regulation of autophagy, and lipid metabolism, as well as its key role in the cellular response to various kinds of stress [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Intracellular pH modulates vimentin remodeling in response to oxidants

Martínez,

González-Jiménez,

Vidal-Verdú

et al. 2023

Preprint

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The intermediate filament protein vimentin plays key roles in the integration of cytoskeletal functions with impact on essential cellular processes including migration, mitosis and autophagy. Moreover, vimentin is involved in pathological processes such as cancer, fibrosis and interaction with pathogens. The vimentin network is finely tuned by posttranslational modifications, among which, those affecting its single cysteine residue (C328) play a critical role not only in vimentin function, but also in its interplay with actin. Interestingly, C328 exhibits a low pKa, which favors the presence of the thiol group in the thiolate form, and therefore its reactivity, at physiological pH. Therefore, C328 reactivity and modifications could be modulated by pH fluctuations in the physiological range. Here we show that indeed, vimentin cysteine oxidation and alkylation, and the subsequent vimentin remodeling, can be modulated as a function of pH, in vitro and in cells. Lowering intracellular pH by several means renders vimentin unresponsive to disruption by oxidants, whereas provoking an intracellular alkalinization exerts a sensitizing effect. The protective effect of low pH appears selective for vimentin since it does not preclude oxidant-elicited disruption of actin or tubulin structures. Importantly, a C328A vimentin mutant is resistant to disruption by oxidants under all pH conditions, highlighting the role of the thiol group at this position in the pH-dependent modulation of vimentin susceptibility to oxidants. Taken together, these results put forward intracellular pH as a key factor modulating redox-dependent vimentin remodeling.

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“…The molecular composition of IFs varies across cell types. For instance, vimentin is expressed in mesenchymal cells, fibroblasts, and endothelial cells, while keratin is expressed in keratinocytes [ 59 ]. Desmin is found in smooth, skeletal, and cardiac muscles [ 60 ].…”

Section: Mechanism Of Mechano-transductionmentioning

confidence: 99%

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

Li,

Ji,

et al. 2024

Military Med Res

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

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Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back

Cited by 20 publications

References 123 publications

Environmental stiffness restores mechanical homeostasis in vimentin-depleted cells

Environmental stiffness restores mechanical homeostasis in vimentin-depleted cells

Intracellular pH modulates vimentin remodeling in response to oxidants

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

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