Biology subjects

Han, Y. L.

Publications and source records attributed to Han, Y. L..

3 recordsLinked to original sources

bioRxiv2022

Recovery of structural integrity of epithelial monolayer in response to massive apoptosis-induced defects

Apoptosis exists ubiquitously in organisms and plays an essential role in maintaining the homeostasis of functional tissues. While the signaling pathway of cell apoptosis has been widely studied, the mechanism of how apoptotic cells regulate the structural homeostasis of a living tissue still remains largely elusive. Using a functional epithelial monolayer as a model system, we find that the integrity of the epithelium is interrupted by apoptosis-induced defects, with an increasing permeability to small molecules across the epithelium. The defects promote a structural reorganization through enhanced cell spreading and migratory dynamics, resulting in a quick recovery of epithelium integrity. Moreover, we show the epithelial monolayer remodeling is driven by local enhanced traction force after apoptosis, which triggers the process of fluidization and mesenchymal-like migration. Our results show the quick recovery of epithelial homeostasis when being interrupted by cell apoptosis, and indicate the importance of apoptosis-induced mechanical force in mediating cell behaviors to maintain the structural integrity of epithelium.

biophysics↗

bioRxiv2021

Nuclear lamin isoforms differentially contribute to LINC complex-dependent nucleocytoskeletal coupling and whole cell mechanics

The ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we show that A- and B-type nuclear lamin isoforms distinctively modulate both nuclear and cellular volume and selectively stabilize the linker of nucleoskeleton and cytoskeleton (LINC) complexes that couple the nucleus to cytoskeletal actin and vimentin. We reveal, further, that loss of each of the four-known lamin isoforms in the mouse embryonic fibroblasts differentially affects cortical and cytoplasmic stiffness as well as cellular contractility, and then propose a LINC complex mediated model that explains these impaired mechanical phenotypes. Finally, we demonstrate that loss of each lamin isoform softens the nucleus in a manner that correlates with loss of heterochromatin. Together, these findings uncover distinctive roles for each lamin isoform in maintaining cellular and nuclear mechanics.

biophysics↗

bioRxiv2020

Tumor invasion as non-equilibrium phase separation

Tumor invasion depends upon properties of both cells and of the extracellular matrix (ECM). Despite ample evidence that cancer cells can modulate their material state during invasion, underlying biophysical mechanisms remain unclear. Here, we show the potential for coexistence of - and transition between - solid-like, fluid-like, and gas-like phases in invading breast cancer spheroids. Epithelial spheroids are nearly jammed and solid-like in the core but unjam at the periphery to invade as a fluid-like collective. Conversely, post-metastatic spheroids are unjammed and fluid-like in the core and - depending on ECM density - can further unjam and invade as gas-like single cells, or re-jam to invade as a fluid-like collective. A novel jamming phase diagram predicts material phases that are superficially similar to inanimate systems at thermodynamic equilibrium, but here arising in living systems, which exist far from equilibrium. We suggest that non-equilibrium phase separation may provide a unifying physical picture of tumor invasion. TWO-SENTENCE SUMMARYUsing tumor spheroids invading into an engineered three-dimensional matrix, we show here that the cellular collective exhibits coexistent solid-like, fluid-like, and gas-like phases. The spheroid interior develops spatial and temporal heterogeneities in material phase which, depending upon cell type and matrix density, ultimately result in a variety of phase separation patterns at the invasive front, as captured by a jamming phase diagram.

biophysics↗