Cell motion-coordinated fibrillar assembly of soluble collagen I to promote MDCK cell branching formation

Zhu

Wang

et al. 2022

Front. Cell Dev. Biol.

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Cell–cell mechanical communications at a large spatial scale (above hundreds of micrometers) have been increasingly recognized in recent decade, which shows importance in tissue-level assembly and morphodynamics. The involved mechanosensing mechanism and resulted physiological functions are still to be fully understood. Recent work showed that traction force sensation in the matrix induces cell communications for self-assembly. Here, based on the experimental model of cell directional migration on Matrigel hydrogel, containing 0.5 mg/ml type I collagen, we studied the mechano-responsive pathways for cell distant communications. Airway smooth muscle (ASM) cells assembled network structure on the hydrogel, whereas stayed isolated individually when cultured on glass without force transmission. Cell directional migration, or network assembly was significantly attenuated by inhibited actomyosin activity, or inhibition of inositol 1,4,5-trisphosphate receptor (IP3R) calcium channel or SERCA pump on endoplasmic reticulum (ER) membrane, or L-type calcium channel on the plasma membrane. Inhibition of integrin β1 with siRNA knockdown reduced cell directional migration and branching assembly, whereas inhibition of cell junctional N-cadherin with siRNA had little effect on distant attractions but blocked branching assembly. Our work demonstrated that the endoplasmic reticulum calcium channels and integrin are mechanosensing signals for cell mechanical communications regulated by actomyosin activity, while N-cadherin is responsible for traction force-induced cell stable connections in the assembly.

Section: Introductionmentioning

confidence: 99%

Mechanical communication-associated cell directional migration and branching connections mediated by calcium channels, integrin β1, and N-cadherin

Zhu

Wang

et al. 2022

Front. Cell Dev. Biol.

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“…Early-stage cancer cell spheroids embedded into COL containing fibroblasts generated force for fibers alignment and CAFs induction(Jung et al, 2020). Our work also showed that motile kidney epithelial cells (MDCK) can actively recruit soluble ECM from the medium to assemble base membrane or COL architectures in directing spherical or tubular tissue formations(Ouyang et al, 2021; Wang et al, 2020). The cell signals of integrin, RhoA, and actomyosin contraction show importance in cells-mediated ECM remodeling(Brownfield et al, 2013; Erdogan et al, 2017).…”

Section: Introductionmentioning

confidence: 69%

Cell Dynamic Mechanics Regulates Large-spatial Isotropic Matrix Modeling with Computational Simulations

Chen

et al. 2022

Preprint

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Tissues and organs often have specific structures or shapes, which developmental process is coordinated by cells and extracellular matrix modeling. The biomechanical aspect how cells and matrix manage large-spatial constructions for tissue morphogenesis or bioengineering has got increasing attentions, while long-range mechanical communications by cells provide certain insights. Previous work has demonstrated the capability of cells in remodeling matrix structures in distance, however, which biophysical mechanistic studies are still pretty conditional. Here, we investigated the underlying dynamic mechanism of collagen I (COL) fibrillary modeling remotely induced by cell traction force, and the involved cellular mechano-signaling. The research designs were based on large arrays of cell clusters, and with incorporated dynamic tractions, the Molecular Dynamics simulations yielded highly matching outcomes with observed COL fiber clustering in experiments based on large-spatial square, parallelogram, and random-style arrays of cell clusters. The further designed single polygons with variable geometries from triangles to hexagons resulted in predicted structures with assembled COL fibers, which space balance was not maintained when introducing additional contraction at their geometrical centers. The cell cytoskeletal integrity (actin filaments, microtubules), actomyosin contractions, and endoplasmic reticulum calcium channels were essential for the remote fiber inductions, whereas membrane mechanosensitive integrin 1 or Piezo1 alone was less critical in fiber assembly. This work provided new mechanistic insights with dynamic and spatial factors on remote induction of matrix modeling by cells at tissue scale, and the involved cellular mechanism. The assembled biomechanical scaffolds based on pre-designs may lead to applications in tissue engineering.

“…These two processes can hardly be decoupled in vivo or through the conventional ECM reconstitution approaches. Our recent work demonstrated that cell motion promotes fibrillary assembly of soluble COL, in supporting the role of cells in ECM scaffold generation 25 . We therefore use the in vitro open‐system assay, and found that spatiotemporal coordination in epithelial morphogenesis and polarization can occur on cell‐assembled ECM in the fluidic phase rather than pre‐assembled ECM in the solid phase.…”

Section: Introductionmentioning

confidence: 85%

“…Our recent work demonstrated that cell motion promotes fibrillary assembly of soluble COL, in supporting the role of cells in ECM scaffold generation. 25 We therefore use the in vitro open-system assay, and found that spatiotemporal coordination in epithelial morphogenesis and polarization can occur on cell-assembled ECM in the fluidic phase rather than pre-assembled ECM in the solid phase. The coordination depends on native topology of the ECM components such as basement membrane (BM) and type I collagen (COL).…”

mentioning

confidence: 99%

Cell‐extracellular matrix interactions in the fluidic phase direct the topology and polarity of self‐organized epithelial structures

Chen

et al. 2021

Cell Proliferation

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Introduction In vivo, cells are surrounded by extracellular matrix (ECM). To build organs from single cells, it is generally believed that ECM serves as scaffolds to coordinate cell positioning and differentiation. Nevertheless, how cells utilize cell‐ECM interactions for the spatiotemporal coordination to different ECM at the tissue scale is not fully understood. Methods Here, using in vitro assay with engineered MDCK cells expressing H2B‐mCherry (nucleus) and gp135/Podocalyxin‐GFP (apical marker), we show in multi‐dimensions that such coordination for epithelial morphogenesis can be determined by cell‐soluble ECM interaction in the fluidic phase. Results The coordination depends on the native topology of ECM components such as sheet‐like basement membrane (BM) and type I collagen (COL) fibres: scaffold formed by BM (COL) facilitates a close‐ended (open‐ended) coordination that leads to the formation of lobular (tubular) epithelium. Further, cells form apicobasal polarity throughout the entire lobule/tubule without a complete coverage of ECM at the basal side, and time‐lapse two‐photon scanning imaging reveals the polarization occurring early and maintained through the lobular expansion. During polarization, gp135‐GFP was converged to the apical surface collectively in the lobular/tubular structures, suggesting possible intercellular communications. Under suspension culture, the polarization was impaired with multi‐lumen formation in the tubules, implying the importance of ECM biomechanical microenvironment. Conclusion Our results suggest a biophysical mechanism for cells to form polarity and coordinate positioning at tissue scale, and in engineering epithelium through cell‐soluble ECM interaction and self‐assembly.