Cell Mechanosensitivity Is Enabled by the LINC Nuclear Complex

Uzer, Gunes; Rubin, Clinton T.; Rubin, Janet

doi:10.1007/s40610-016-0032-8

Cited by 46 publications

(38 citation statements)

References 161 publications

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“…Cells must sense, respond, and adapt to their physical environments at every level (molecular, cellular, tissue, organ and organism). Cells respond to mechanical cues by initiating signals that result in adaptations in cytoskeletal architecture and gene expression [ 46 ]. Adhesion to the ECM is achieved by all types of adherent cells.…”

Section: Adhesion Of Cells To Ecm and Mechanotransductionmentioning

confidence: 99%

Micro and Nanofabrication methods to control cell-substrate interactions and cell behavior: A review from the tissue engineering perspective

Ermis

Antmen

Hasırcı

2018

Bioactive Materials

233

169

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Cell-substrate interactions play a crucial role in the design of better biomaterials and integration of implants with the tissues. Adhesion is the binding process of the cells to the substrate through interactions between the surface molecules of the cell membrane and the substrate. There are several factors that affect cell adhesion including substrate surface chemistry, topography, and stiffness. These factors physically and chemically guide and influence the adhesion strength, spreading, shape and fate of the cell. Recently, technological advances enabled us to precisely engineer the geometry and chemistry of substrate surfaces enabling the control of the interaction cells with the substrate. Some of the most commonly used surface engineering methods for eliciting the desired cellular responses on biomaterials are photolithography, electron beam lithography, microcontact printing, and microfluidics. These methods allow production of nano- and micron level substrate features that can control cell adhesion, migration, differentiation, shape of the cells and the nuclei as well as measurement of the forces involved in such activities. This review aims to summarize the current techniques and associate these techniques with cellular responses in order to emphasize the effect of chemistry, dimensions, density and design of surface patterns on cell-substrate interactions. We conclude with future projections in the field of cell-substrate interactions in the hope of providing an outlook for the future studies.

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Section: Adhesion Of Cells To Ecm and Mechanotransductionmentioning

confidence: 99%

Micro and Nanofabrication methods to control cell-substrate interactions and cell behavior: A review from the tissue engineering perspective

Ermis

Antmen

Hasırcı

2018

Bioactive Materials

233

169

View full text Add to dashboard Cite

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“…FHOD1 formin 51 , for example, has recently been shown to interact with Nesprin-2 and may be important for nuclear positioning and maintaining coupling between the nucleus and cytoskeleton. Further, LINC complexes may also be involved in formin mediated perinuclear and intranuclear actin dynamics 52 53 , suggesting that formins play a yet to be determined role in LINC mediated LIV mechanotransduction. Our data demonstrated that the expression levels of Nesprin-2, the actin-binding element of the LINC complex as well as the nuclear scaffolding protein LaminA/C experienced the greatest upregulation at Day 14 when exposed to horizontal 100 Hz-0.15 g LIV.…”

Section: Discussionmentioning

confidence: 99%

Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

Pongkitwitoon

Uzer

Rubin

et al. 2016

Sci Rep

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Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and hypothesized that the confined cytoskeletal configuration imposed by 2D culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV). All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and upregulated genes associated with cytoskeletal structure. The cellular response was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in the horizontal plane. Horizontal but not vertical LIV realigned the cell cytoskeleton, culminating in increased cell stiffness. Our results show that applying very small oscillatory motions within the primary cell attachment plane, rather than perpendicular to it, amplifies the cell’s response to LIV, ostensibly facilitating a more effective transfer of intracellular forces. Transcriptional and structural changes in particular with horizontal LIV, together with the strong frequency dependency of the signal, emphasize the importance of intracellular cytoskeletal configuration in sensing and responding to high-frequency mechanical signals at low intensities.

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“…The LINC complex was discovered relatively recently, but has been shown to be highly conserved in eukaryotes, with myriad functions as described in numerous reviews [4][5][6][7][8][9]. These LINC-mediated functions include regulation of nuclear shape and position [10,11], mechanosensory signal transduction [12], control of cell division, intranuclear architecture and gene regulation [13][14][15], and the specialized behavior of meiotic chromosomes to ensure segregation and fertility [16][17][18]. The two core LINC components are the inner nuclear membrane (INM) SUN-domain proteins [19,20] and outer nuclear membrane (ONM) KASH-domain proteins [21].…”

Section: Introductionmentioning

confidence: 99%

MLKS2 is an ARM domain and F-actin-associated KASH protein that functions in stomatal complex development and meiotic chromosome segregation

Gumber

McKenna

Tolmie

et al. 2019

Nucleus

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The linker of nucleoskeleton and cytoskeleton (LINC) complex is an essential multi-protein structure spanning the eukaryotic nuclear envelope. The LINC complex functions to maintain nuclear architecture, positioning, and mobility, along with specialized functions in meiotic prophase and chromosome segregation. Members of the LINC complex were recently identified in maize, an important scientific and agricultural grass species. Here we characterized Maize LINC KASH AtSINE-like2, MLKS2 , which encodes a highly conserved SINE-group plant KASH protein with characteristic N-terminal armadillo repeats (ARM). Using a heterologous expression system, we showed that actively expressed GFP-MLKS2 is targeted to the nuclear periphery and colocalizes with F-actin and the endoplasmic reticulum, but not microtubules in the cell cortex. Expression of GFP-MLKS2, but not GFP-MLKS2ΔARM, resulted in nuclear anchoring. Genetic analysis of transposon-insertion mutations, mlks2-1 and mlks2-2 , showed that the mutant phenotypes were pleiotropic, affecting root hair nuclear morphology, stomatal complex development, multiple aspects of meiosis, and pollen viability. In male meiosis, the mutants showed defects for bouquet-stage telomere clustering, nuclear repositioning, perinuclear actin accumulation, dispersal of late prophase bivalents, and meiotic chromosome segregation. These findings support a model in which the nucleus is connected to cytoskeletal F-actin through the ARM-domain, predicted alpha solenoid structure of MLKS2. Functional conservation of MLKS2 was demonstrated through genetic rescue of the misshapen nuclear phenotype of an Arabidopsis (triple- WIP ) KASH mutant. This study establishes a role for the SINE-type KASH proteins in affecting the dynamic nuclear phenomena required for normal plant growth and fertility. Abbreviations : FRAP: Fluorescence recovery after photobleaching; DPI: Days post infiltration; OD: Optical density; MLKS2: Maize LINC KASH AtSINE-like2; LINC: Linker of nucleoskeleton and cytoskeleton; NE: Nuclear envelope; INM: Inner nuclear membrane; ONM: Outer nuclear membrane

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Cell Mechanosensitivity Is Enabled by the LINC Nuclear Complex

Cited by 46 publications

References 161 publications

Micro and Nanofabrication methods to control cell-substrate interactions and cell behavior: A review from the tissue engineering perspective

Micro and Nanofabrication methods to control cell-substrate interactions and cell behavior: A review from the tissue engineering perspective

Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

MLKS2 is an ARM domain and F-actin-associated KASH protein that functions in stomatal complex development and meiotic chromosome segregation

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