Biology subjects

Wuergezhen, D.

Publications and source records attributed to Wuergezhen, D..

3 recordsLinked to original sources

bioRxiv2024

Epithelium Stratifies via Nucleation and Growth Induced by Foam-Geometric Instability

The epithelium undergoes stratification, transitioning from a monolayer to a multilayer structure, across broad phenomena. Recent studies have identified several cell behaviors as triggers, including junctional tension, cell density and geometry, and topological defects. However, how these factors drive stratification throughout the entire epithelium remains poorly understood. Here, we report a mechanism underlying epithelial stratification that mirrors the physics of phase transition. Combining cell culture with three-dimensional vertex modeling, we demonstrate that epithelial stratification is analogous to a structural phase transition driven by the nucleation-growth process, i.e., multilayer origins dispersedly appear and expand across the epithelium via unordered intermediate states. This transition is induced by a mechanical instability inherent in the foam-like geometry of the epithelium. Moreover, the nucleation-growth concept applies to embryonic skin development and intestinal cancer transformation. These findings conceptualize epithelial stratification as a form of a phase transition governed by foam mechanics, offering a physical perspective on various epithelial developments.

biophysics↗

bioRxiv2024

Ex vivo SIM-AFM measurements reveal the spatial correlation of stiffness and molecular distributions in 3D living tissue

Living tissues each exhibit a distinct stiffness, which provides cells with key environmental cues that regulate their behaviors. Despite this significance, our understanding of the spatiotemporal dynamics and the biological roles of stiffness in three-dimensional tissues is currently limited due to a lack of appropriate measurement techniques. To address this issue, we propose a new method combining upright structured illumination microscopy (USIM) and atomic force microscopy (AFM) to obtain precisely coordinated stiffness maps and biomolecular fluorescence images of thick living tissue slices. Using mouse embryonic skin as a representative tissue with mechanically heterogeneous structures inside, we validate the measurement principle of USIM-AFM. Live measurement of tissue stiffness distributions revealed the highly heterogeneous mechanical nature of embryonic skin as well as the role of collagens in maintaining its integrity. Furthermore, quantitative comparisons of stiffness distributions of preserved tissue samples unveiled the distinct impacts of conventional tissue preservation techniques on the tissue stiffness pattern. This series of experiments highlights the importance of live mechanical testing of tissue-scale samples. Our USIM-AFM technique provides a new methodology to reveal the dynamic nature of tissue stiffness and its correlation with biomolecular distributions in live tissues and thus could serve as a technical basis for exploring tissue-scale mechanobiology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/595975v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@8a32f5org.highwire.dtl.DTLVardef@117a350org.highwire.dtl.DTLVardef@e2fb99org.highwire.dtl.DTLVardef@1f41d24_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Col4a2-eGFP mouse model reveals the molecular and functional dynamics of basement membrane remodelling in hair follicle morphogenesis

The precisely controlled remodelling of the basement membrane (BM) is considered vital for morphogenesis. However, the molecular and tissue-level dynamics of the BM during morphogenesis and their functional significance remain largely unknown, especially in mammals, due to limited visualization tools. We developed knock-in mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we revealed a spatial gradient in the turnover rate of COL4A2 that is closely coupled with the BM expansion rate. The proliferation of epithelial progenitors coincided with the increased expansion of their underlying BM. Epithelial progenitors displaced with directionally expanding BM, but did not actively migrate on stable BM. The addition of a matrix metalloproteinase inhibitor delayed the turnover of COL4A2, restrained the expansion of the BM, and induced a directional shift in the division angle of epithelial progenitors, altering the hair follicle morphology. Our findings revealed spatially distinct BM dynamics within the continuous epithelial BM and affirmed their significance in orchestrating the proliferation, movement and fate of progenitor cells, as well as the macro-level shape of organs during development.

developmental biology↗