Biology subjects

Lin, S.-Z.

Publications and source records attributed to Lin, S.-Z..

7 recordsLinked to original sources

bioRxiv2024

A multicellular actin star network underpins epithelial organization and connectivity

Epithelial tissues serve as physical barriers against various external pressures yet remarkably maintain structural stability. Various cellular apparatus including bicellular junction and actomyosin network contribute to the epithelial integrity, packing and remodelling. Although their role in morphogenetic and mechanical processes have been extensively studied during embryogenesis and disease development, their synergistic effects in maintaining tissue organization and connection remain poorly understood. In this study, we discovered a tissue-scale actomyosin network connected through bicellular junctions and manifested in the villi of adult murine intestinal tissue. Later we reproduced such supracellular structure in the differentiated compartment of ex vivo intestinal epithelium model. The self-organized actomyosin networks comprised individual actin nodes in each hexagonal cell at the epithelial base with six radial actin branches, presenting an actin star unit. The repeated units were connected through the bicellular junctions, forming a large, multicellular array covering the differentiated domains. Functionally, actin stars contribute to epithelial morphological stability by maintaining cell hexagonality and packing, thereby preserving the solid-like order of the epithelium. Laser ablation experiments validate a modified vertex theoretical model that connects the emergence of such solid-like order to the onset of tension along the actin star branches. Actin stars also acted as locks at the basal side minimizing protrusive activity in the epithelial layer, hindering cell migration and disorganization of the epithelial tissue. Altogether, the supracellular actin star network constitutes a basal biomechanical apparatus coordinating epithelial tissue stability and organization.

cell biology↗

bioRxiv2023

E-cadherin-dependent phosphorylation of EGFR governs a homeostatic feedback loop controlling intercellular junction viscosity and collective migration modes.

Actomyosin tension has been shown to be a ubiquitous driver of tissue morphogenesis1, 2. The Rho pathway, a prominent regulatory network influencing cortical tension, plays a central role in both tissue reorganisation and cell migration3-6. While viscous dissipation in the actin network is commonly regarded as a constant passive parameter in cell migration in both 2D and 3D contexts, there is limited knowledge concerning the regulation of dissipative forces arising from viscous drag between cells during collective rearrangement. Here, we found that the phosphorylation of Epithelial Growth Factor Receptor (EGFR) downstream of de novo E-cadherin adhesion7, 8 orchestrates a feedback loop, thereby governing intercellular viscosity via the Rac pathway regulating actin dynamics. Our findings highlight how the E-cadherin-dependent EGFR activity controls the migration mode of collective cell movements independently of intercellular tension. Combining molecular cell biology, micropatterning, and in silico simulation, our work suggests the existence of a regulatory loop by which cells can tune junctional actin viscosity, with implications for the phenomenology of morphogenetic movements.

cell biology↗

bioRxiv2022

Chinese fir genome and the evolution of gymnosperms

Seed plants comprise angiosperms and gymnosperms. The latter includes gnetophytes, cycads, Ginkgo, and conifers. Conifers are distributed worldwide, with 630 species distributed across eight families and 70 genera. Their distinctiveness has triggered much debate on their origin, evolution, and phylogenetic placement among seed plants. To better understand the evolution of gymnosperms and their relation to other seed plants, we report here a high-quality genome sequence for a tree species, Chinese fir (Cunninghamia lanceolata), which has excellent timber quality and high aluminum adaptability and is a member of Cupressaceae with high levels of heterozygosity. We assembled an 11.24 Gb genome with a contig N50 value of 2.15 Mb and anchored the 10.89 Gb sequence to 11 chromosomes. Phylogenomic analyses showed that cycads sister to Ginkgo, which place to sister in all gymnosperm lineages, and Gnetales within conifers sister to Pinaceae. Whole-genome duplication (WGD) analysis showed that the ancestor of seed plants has differentiated into angiosperms and gymnosperms after having experienced a WGD event. The ancestor of extant gymnosperm has experienced a gymnosperm-specific WGD event and the extant angiosperms do not share a common WGD before their most recent common ancestor diverged into existing angiosperms lineages. Analysis of the MADS-box gene family of C. lanceolata revealed the developmental mechanism of the reproductive organs in C. lanceolata, which supported the (A)B(C) model of the development of gymnosperms reproductive organs. In addition, astringent seeds and shedding of whole branches (with withered leaves) might be a strategy of C. lanceolata that evolved during long-term adaptation to an aluminum-rich environment. The findings also reveal the molecular regulation mechanism of shade tolerance in C. lanceolata seedlings. Our results improve the resolution of ancestral genomic features within seed plants and the knowledge of genome evolution and diversification of gymnosperms.

genomics↗

bioRxiv2022

Alcanivorax borkumensis Biofilms Enhance Oil Degradation By Interfacial Tubulation

Alcanivorax borkumensis are prominent actors in oil spill bioremediation; however, the interfacial dynamics of their biofilms and its role in oil degradation remain unclear. Longitudinal tracking of biofilm-covered oil microdroplets using microfluidics reveals a spontaneous morphological transition from a thick biofilm phenotype to a thin dendritic phenotype optimized for high oil consumption rates. We show experimentally that biofilm dendrites emerge from aster-like nematic defects in the thin biofilms. We develop a theoretical model that elucidates the transition between phenotypes, linking tubulation to decreased interfacial tension and increased cell hydrophobicity, which we verify experimentally. We demonstrate positional control over the nematic defects on the droplets using microfluidics, causing the biofilm to dimple the droplets. Our results reveal how A. borkumensis biofilms utilize topological defects to increase oil access to achieve superior oil consumption rates, which may be a general strategy in oil-consuming bacteria. ONE SENTENCE SUMMARYA. borkumensis adapt their interfacial properties over time to evolve their biofilm phenotype and increase their oil consumption

biophysics↗

bioRxiv2022

Two-point optical manipulation reveals mechanosensitive remodeling of cell-cell contacts in vivo

Biological tissues acquire reproducible shapes during development through dynamic cell behaviors. These events involve the remodeling of cell contacts driven by active cytoskeletal contractile forces. However how cell-cell contacts remodel remains poorly understood because of lack of tools to directly apply forces at cell-cell contacts to produce their remodeling. Here we develop a dual-optical trap manipulation method to impose different force patterns on cell-cell contacts in the early epithelium of the Drosophila embryo. Through different push and pull manipulations at the edges of junctions, the technique allows us to produce junction extension and junction shrinkage. We use these observations to constrain and specify vertex-based models of tissue mechanics, incorporating negative and positive mechanosensitive feedback depending on the type of remodeling. We show that Myosin-II activity responds to junction strain rate and facilitates full junction shrinkage. Altogether our work provides insight into how stress produces efficient deformation of cell-cell contacts in vivo and identifies unanticipated mechanosensitive features of their remodeling. Significance statementThe highly organized tissues and organs that form our body emerge from internal dynamic activities at the cellular level. Among such activities, cell shape changes and cell rearrangement, cell extrusion and cell division sculpt epithelial tissues into elongated sheets, tubes and spherical cavities. Remodeling of cell-cell contacts, powered by actomyosin contractility, is key to all these transformations. Although much is known about the molecular machinery and biochemical signals that regulate remodeling of cell contacts, there is a lack of approaches to directly probe the mechanics of cell contacts and therefore assess their ability to resist or deform in response to mechanical loads. We developed an experimental technique to manipulate and exert contractile and extensile forces to cell-cell junctions. Our results lead to a specific physical model of junctional mechanics, with implications in the modeling of collective cell behavior in epithelial tissues.

biophysics↗

bioRxiv2022

Mechanical stress driven by rigidity sensing governs epithelial stability

Epithelia act as a barrier against environmental stress and abrasion and in vivo they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneous hole formation when grown on soft substrates. Substrate stiffness triggers an unanticipated mechanical switch of epithelial monolayers from tensile on soft to compressive on stiff substrates. Through active nematic modelling, we find unique patterns of cell shape texture called nematic topological defects that underpin large isotropic stress fluctuations at certain locations thereby triggering mechanical failure of the monolayer and hole opening. Our results show that substrate stiffness provides feedback on monolayer mechanical state and that topological defects can trigger stochastic mechanical failure, with potential application towards a mechanistic understanding of compromised epithelial integrity in bacterial infection, tumor progression and morphogenesis.

biophysics↗

bioRxiv2022

Drosophila Mechanical Nociceptors Preferentially Sense Localized Poking

Mechanical nociception is an evolutionarily conserved sensory process required for the survival of living organisms. Previous studies have revealed much about the neural circuits and key sensory molecules in mechanical nociception, but the cellular mechanisms adopted by nociceptors in force detection remain elusive. To address this issue, we study the mechanosensation of a fly larval nociceptor (class IV da neurons, c4da) using a customized mechanical device. We find that c4da are sensitive to mN-scale forces and make uniform responses to the forces applied at different dendritic regions. Moreover, c4da showed a greater sensitivity to more localized forces, consistent with them being able to sense the poking of sharp objects, such as wasp ovipositor. Further analysis reveals that high morphological complexity, mechanosensitivity to lateral tension and active signal propagation in the dendrites altogether facilitate the mechanosensitivity and sensory features of c4da. In particular, we discover that Piezo and Ppk1/Ppk26, two key mechanosensory molecules, make differential but additive contributions to the mechanosensation of c4da. In all, our results provide updates into understanding how c4da process mechanical signals at the cellular level and reveal the contributions of key molecules.

neuroscience↗