title: Substrate Stiffness Regulates the Development of Left-Right Asymmetry in Cell Orientation.
abstract: Left-right (LR) asymmetry of tissue/organ structure is a morphological feature essential for many tissue functions. The ability to incorporate the LR formation in constructing tissue/organ replacement is important for recapturing the inherent tissue structure and functions. However, how LR asymmetry is formed remains largely underdetermined, which creates significant hurdles to reproduce and regulate the formation of LR asymmetry in an engineering context. Here, we report substrate rigidity functioning as an effective switch that turns on the development of LR asymmetry. Using micropatterned cell-adherent stripes on rigid substrates, we found that cells collectively oriented at a LR-biased angle relative to the stripe boundary. This LR asymmetry was initiated by a LR-biased migration of cells at stripe boundary, which later generated a velocity gradient propagating from stripe boundary to the center. After a series of cell translocations and rotations, ultimately, an LR-biased cell orientation within the micropatterned stripe was formed. Importantly, this initiation and propagation of LR asymmetry was observed only on rigid but not on soft substrates, suggesting that the LR asymmetry was regulated by rigid substrate probably through the organization of actin cytoskeleton. Together, we demonstrated substrate rigidity as a determinant factor that mediates the self-organizing LR asymmetry being unfolded from single cells to multicellular organization. More broadly, we anticipate that our findings would pave the way for rebuilding artificial tissue constructs with inherent LR asymmetry in the future.
authors.forename: Yuanye
authors.initials: Y
authors.lastname: Bao
authors.forename: Yaozhun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: CityU Shenzhen Research Institute , Shenzhen 518057, China.
authors.forename: Miu Ling
authors.initials: ML
authors.lastname: Lam
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Ninghao
authors.initials: N
authors.lastname: Zhu
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.affiliation: CityU Shenzhen Research Institute , Shenzhen 518057, China.
authors.forename: Raymond H W
authors.initials: RH
authors.lastname: Lam
authors.affiliation: CityU Shenzhen Research Institute , Shenzhen 518057, China.
authors.forename: Ting-Hsuan
authors.initials: TH
authors.lastname: Chen
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D048429:Cell Size; D004129:Dimethylpolysiloxanes; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D013500:Surface Tension
chemical_list: D015815:Cell Adhesion Molecules; D004129:Dimethylpolysiloxanes
keywords: cell chirality; cell orientation; left−right asymmetry; micropatterning; migration; stiffness