Biology subjects

Chew, T. G.

Publications and source records attributed to Chew, T. G..

4 recordsLinked to original sources

bioRxiv2021

Robust maintenance of cell surface tension in mitosis by RhoA-driven myosin II mechanoresponse

Non-muscle myosin II (NMII) is a force-generating mechanosensitive enzyme that responds to mechanical forces exerted on cells. Mechanoresponse of NMIIs confers mechanical adaptability to cells growing and dividing in a physically complex microenvironment. In response to mechanical forces, NMIIs mechanoaccumulate at the cell cortex with applied stress. Much less is known about how NMII mechanoaccumulation is mechanistically regulated. In this study, we subject cells in mitosis to compressive forces and show that mitotic cells promote active RhoA mechanoaccumulation, and via ROCK signaling, activate and stabilize NMIIB at the cell cortex. In line with RhoA in activating the myosin motor activity, we further show that the motor activity driving actin filament translocation, but not just the actin-binding function of NMIIB plays a dominant regulatory role in NMIIB mechanoaccumulation. Thus, the motor activity coordinates structural movement and nucleotide state changes to fine-tune actin-binding affinity optimal for NMIIs to generate and respond to forces.

cell biology↗

bioRxiv2021

Myosin turnover controls actomyosin contractile instability

Actomyosin contractile force is harnessed for diverse functions, from cell division to morphogenesis during development. However, actomyosin contractility is intrinsically unstable to self-reinforcing spatial variations that destroy actomyosin architecture if unopposed. The full instability was rarely observed, and how cells control the instability is not established. Here, we observed the instability run its full course in isolated cytokinetic contractile rings lacking component turnover. Myosin II aggregated hierarchically into aggregates of growing size and separation up to a maximum. Molecularly explicit simulations reproduced hierarchical aggregation that precipitated tension loss and ring fracture, and identified the maximum separation as the length of actin filaments mediating mechanical communication between aggregates. Late stage simulated aggregates had aster-like morphology with polarity sorted actin, similar to late stage actomyosin systems in vitro. Our results suggest myosin II turnover controls actomyosin contractile instability in normal cells, setting myosin aggregate size and intercepting catastrophic hierarchical aggregation and fracture.

cell biology↗

bioRxiv2020

High-resolution architecture of human epiphysis formation

Human limb skeletal system consists of both bone and cartilage which originated from fetal cartilage. However, the roadmap of chondrocyte divergent differentiation to bone and articular cartilage has yet to be established. Epiphysis possesses articular cartilage, growth plate and the secondary ossification center (SOC), making it an ideal model to uncover the trajectory of chondrocyte divergent differentiation. Here, we mapped differentiation trajectory of human chondrocyte during postnatal finger epiphysis development by using single-cell RNA sequencing. Our results uncovered that chondroprogenitors have two differentiation pathways to hypertrophic chondrocytes during ossification, and one pathway to articular chondrocytes for formation of cartilages. Interestingly, we found that, as an addition to the known typical endochondral ossification path from resting, proliferative to hypertrophic chondrocytes, there was a bypass by which chondroprogenitors differentiate into hypertrophic chondrocytes without proliferative stage. Furthermore, our results revealed two new chondrocyte subpopulations (bypass chondrocytes as it appeared in the ossification bypass, and ID1+ chondroblasts in articular chondrocyte path) during postnatal epiphysis development in addition to six well-known subpopulations. Overall, our study provides a comprehensive roadmap of chondrocyte differentiation in human epiphysis thereby expanding the knowledge of bone and articular cartilage, which could be utilized to design biotherapeutics for bone and articular cartilage regeneration.

developmental biology↗

bioRxiv2020

Inhibition of cell membrane ingression at the division site by cell wall in fission yeast

Eukaryotic cells assemble an actomyosin ring during cytokinesis to function as a force-generating machine to drive membrane invagination, and to counteract the intracellular pressure and the cell surface tension. It is unclear whether additional factors such as the extracellular matrix (cell wall in yeasts and fungi) affect the actomyosin ring contraction. While studying the fission yeast {beta}-glucan synthase mutant cps1-191, which is defective in division septum synthesis and actomyosin ring contraction, we found that significantly weakening of the extracellular glycan matrix caused the spheroplasts to divide at the non-permissive condition. This division was dependent on a functional actomyosin ring and vesicular trafficking, but independent of normal septum synthesis. cps1-191 cells with weakened extracellular glycan matrix divide non-medially with a much slower ring contraction rate compared to wild type cells under similar conditions, which we term as cytofission. Interestingly, the high turgor pressure appears to play minimal roles in inhibiting ring contraction in cps1-191 mutants as decreasing the turgor pressure alone does not enable cytofission. We propose that during cytokinesis, the extracellular glycan matrix restricts actomyosin ring contraction and membrane ingression, and remodeling of the extracellular components through division septum synthesis relieves the inhibition and facilitates actomyosin ring contraction.

cell biology↗