Nanowire Magnetoscope Reveals a Cellular Torque with Left–Right Bias

Liu, Wei; Bao, Yuanye; Lam, Miu Ling; Xu, Ting; Xie, Kai; Man, Hin Sum; Chan, Edward Y.; Zhu, Ninghao; Lam, Raymond H. W.; Chen, Ting‐Hsuan

doi:10.1021/acsnano.6b01142

Cited by 34 publications

(53 citation statements)

References 48 publications

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“…To visualize the actin filaments, we applied fluorescence staining of actin on different substrates. Circular micropatterns were used for the analysis of the actin cytoskeleton because they provide a geometric confinement of the cell shape that highlights the classification of the transverse arc and dorsal stress fibers of individual cells [ 7 ]. When cells were cultured in circular micropatterns on a rigid substrate, clear actin stress fibers can be observed ( Figure 5 a).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, we further demonstrated that actin stress fibers play a vital role in the formation of a chiral pattern of C2C12 cells. Actin stress fibers can generate a contractile force, which controls the formation of focal adhesion [ 7 , 9 , 15 ]. Meanwhile, actin stress fibers can be regulated by the substrate stiffness, which is also responsible for cell mechanosensing.…”

Section: Discussionmentioning

confidence: 99%

“…Skeletal muscle is the largest tissue in mammalian organisms. The appropriate function of skeletal muscle is to provide physical support essential for the metabolism of individuals [ 6 , 7 ]. When regenerating skeletal muscle in vitro, myoblasts should differentiate and form well-aligned myotubes as aligned muscle bundles in vivo [ 8 ], which requires the expression of the LR asymmetry to determine the specific orientation of the skeletal muscle cells.…”

Section: Introductionmentioning

confidence: 99%

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Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate

et al. 2017

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Reconstitution of tissue morphology with inherent left–right (LR) asymmetry is essential for tissue/organ functions. For skeletal muscle, the largest tissue in mammalian organisms, successful myogenesis requires the regulation of the LR asymmetry to form the appropriate muscle alignment. However, the key factor for reproducing the LR asymmetry of skeletal tissues in a controllable, engineering context remains largely unknown. Recent reports indicate that cell chirality may underlie the LR development in tissue morphogenesis. Here, we report that a rigid substrate is required for the chirality of skeletal muscle cells. By using alternating micropatterned cell-adherent and cell-repellent stripes on a rigid substrate, we found that C2C12 skeletal muscle myoblasts exhibited a unidirectional tilted orientation with respect to the stripe boundary. Importantly, such chiral orientation was reduced when soft substrates were used instead. In addition, we demonstrated the key role of actin stress fibers in the formation of the chiral orientation. This study reveals that a rigid substrate is required for the chiral pattern of myoblasts, paving the way for reconstructing damaged muscle tissue with inherent LR asymmetry in the future.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate

et al. 2017

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“…We next tested whether the hMSC chirality exists in nucleus rotation of single cells. [13,21] Individual cells were seeded onto cell-adherent circular patterns surrounded by pluronic coating ( Figure 1D). With reference to the long-axis of cell nucleus, the transient angular velocity of cell nucleus was recorded at each 10 min interval, and the percentages of transient CW and ACW rotation within the observation duration were compared to determine the rotational bias ( Figure 1D).…”

Section: Chirality Of Hmscsmentioning

confidence: 99%

“…Previous findings revealed that, when cells are cultured on circular islands, their actin cytoskeleton forms a CW-or ACW-biased swirl pattern of dorsal stress fibers that are unidirectionally tilted with a tangential shift of transverse arc. [13,15,21,43] After the rotational assay on gear patterns mentioned above, the cells were fixed and stained ( Figure 1F). Automated image processing was used to analyze the tilting angle of actin filament with respect to the radial axis of each cell.…”

Section: Chirality Of Hmscsmentioning

confidence: 99%

Early Committed Clockwise Cell Chirality Upregulates Adipogenic Differentiation of Mesenchymal Stem Cells

Bao

Chu

et al. 2020

Adv. Biosys.

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determine the LR asymmetry in morphogenesis. [2] For example, chirality has been found in Xenopus egg cortex before fertilization, [1] and can be passed down to more differentiated cells that establish LR body axis of animal body plan, [7] organ distribution, [8-10] and epithelial movement that leads to axial torsion and overall handedness of hindgut. [11,12] For specialized adult cells derived from somatic tissue, footprints of cell chirality can still be seen by their ability of generating cellular torque, [6,13] migration with LR bias, [14-16] or forming specific alignment in the multicellular level. [15,17,18] Through cell-cell communication, the chiral behavior causes LR-biased cell assembly of multicellular structure [15] and regulates permeability of intercellular junctions. [19] Clearly, cell chirality can be manifested in diverse forms and coordinate different morphogenic dynamics, resulting in distinct forms of tissue and organ architecture. Actin cytoskeleton plays an important role in cell chirality. When cultured on micropatterned substrate, the accumulation of actomyosin stress fibers at micropattern boundary is essential to activate the LR bias in cell migration and orientation. [15,17] Molecular studies suggest helical motion of actin filament as the underlying mechanism for the chirality at cellular level. [20,21] Functioning as a built-in machinery, actomyosin cytoskeleton allows chiral nucleus rotation of single cell [21] and generation of cellular torque with rotational bias. [13] Through a series of amplification process, the actin chirality ultimately determines the symmetry breaking in early embryonic development, [1,7,22] cardiac looping, [4,8,23] and organ laterality [9] in vivo. To give rise to such diverse forms of cell chirality, cell differentiation should play a role. [13,15,17] Cell differentiation is a process coupling with chemical [24] and physical factors. [25-27] Based on variation of key proteins in cytoskeleton, [28] cytoskeleton can be changed at early stage of cell differentiation, as shown by upregulation of cytoskeletal contractility [29] and cell morphological features, which can even forecast the cell lineage fate. [28] It suggests that cytoskeletal components, particularly actin, may early respond to the induction of cell differentiation and then actively participate the signal cascades to engage cell fate. Evidences can be found by regulation of cell differentiation via changed cell shape and cell spreading by physical cues [30-38]

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Cell Chirality as a Novel Measure for Cytotoxicity

Zhang

Wan

2021

Advanced Biology

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Cytotoxicity assessment has great importance in both research and pharmaceutical development. The mainstream in vitro cytotoxicity assays are mostly biochemical assays that evaluate a specific cellular activity such as proliferation and apoptosis. Few assays assess toxicity by characterizing overall functional outcomes in cellular physiology such as multicellular morphogenesis. The intrinsic cellular chiral bias (also known as cell chirality, left‐right asymmetry, or handedness), which determines cellular polarization along the left‐right axis, is demonstrated to play important roles in development and disease. This chiral property of cells gives insights not only into functions of individual cells, such as motility and polarity but also into emerging behaviors of cell clusters, such as collective cell migration. Therefore, cell chirality characterization can be potentially used as a biomarker for assessing the overall effects of pharmaceutical drugs and environmental factors on the health of the cell. In this review article, the current in vitro techniques for cell chirality characterization and their applications are discussed and the advantages and limitations of these cell chirality assays as potential tools for detecting cytotoxicity are discussed.

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Nanowire Magnetoscope Reveals a Cellular Torque with Left–Right Bias

Cited by 34 publications

References 48 publications

Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate

Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate

Early Committed Clockwise Cell Chirality Upregulates Adipogenic Differentiation of Mesenchymal Stem Cells

Cell Chirality as a Novel Measure for Cytotoxicity

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