Biology subjects

Lu, T. B.

Publications and source records attributed to Lu, T. B..

4 recordsLinked to original sources

bioRxiv2026

Theca cell mechanosensing and regulation of follicular extracellular matrix during ovarian follicle development

Mammalian folliculogenesis is essential for female hormonal regulation and successful reproduction. While the steroidogenic functions of theca cells (TCs) have been implicated in ovarian diseases and infertility, the physico-structural properties of TCs and their associated extracellular matrix (ECM), or theca matrix, remain poorly understood. Using murine ovaries, we show that a stiff basement membrane (BM) and theca matrix constitute a mechanically instructive niche that modulates TC proliferation and Yes-associated protein (YAP) signalling in secondary follicles. We identify hyaluronic acid (HA) as a key matrix component that is actively secreted by contractile TCs. The HA scaffold, in turn, regulates TC proliferation, YAP signalling and motility, and is required for overall follicle growth. We showed that stiffer substrates enhance YAP nuclear transport in TCs, while mechanical stretch, cell packing, and curvature affect TC proliferation. In addition, TCs exhibit directed migration towards regions of positive curvature. Together, this study reveals a mechanochemical feedback mechanism that establishes TC mechanics and HA as key regulators of theca matrix formation that is essential for mammalian folliculogenesis. SIGNIFICANCEThe structural properties and mechanical functions of the basement membrane and theca cell-matrix encapsulating mammalian ovarian follicles are poorly understood. Our findings reveal that during early stage of follicle development, the basement membrane remains thin and stiff, while the theca cells actively secrete hyaluronic acid in a contractility-dependent manner. The hyaluronic acid scaffold, in turn, regulates theca cell YAP signalling, proliferation and motility that are required for functional growth of follicles. We further showed that the theca cells are mechanosensitive and fine-tune their proliferative capacity and Hippo pathways in response to substrate stiffness, stretch and curvature. Together, our study uncovers mechanoregulatory feedback between theca cells and associated extracellular matrix, offering new insights into environmental control of folliculogenesis in female reproduction.

developmental biology↗

bioRxiv2025

Critical phenomenon underlies de novo luminogenesis during mammalian follicle development

A key process during mammalian folliculogenesis is the formation of a fluid-filled antrum around the oocyte. While it is known that the antrum is critical for oocyte maturation and the eventual ovulation, the detailed process underlying de novo luminogenesis remains poorly understood. In this study, we investigated the spatiotemporal dynamics of lumen growth and the cellular mechanism driving this process, using advanced microscopy, molecular perturbations and computational modelling. We found that in secondary follicles, the interstitial gaps exist in a near-critical regime, characterised by a highly dynamic and interconnected fluid network with gap size obeying a power-law distribution. Above a critical size of 180 m, we observed an onset of cell death and the emergence of a stably growing dominant fluid cavity resembling phase separation. By modelling the granulosa cells and the interstitial fluid as a binary fluid, we reproduced the near-critical and phase-separated regimes and found that a spatial gradient of cell-fluid interfacial tension, as observed experimentally, is sufficient to robustly maintain the secondary follicles in a near-critical state. Reducing cell-fluid interfacial tension globally by weakening the cell-cell adhesion between granulosa cells leads to fragmentation of fluid and growth arrest of the dominant cavity, as predicted by the model. Importantly, perturbing the critical state in secondary follicles leads to impaired follicle growth. Altogether, our study reveals how collective spatiotemporal regulation of cell junction mechanics and cell death can contribute to the effective transition between distinct regimes of fluids, which are indispensable for functional maturation of follicles.

developmental biology↗

bioRxiv2025

Analysis of the surface topology of respiratory syncytial virus particles that form on the surface of virus-infected cells.

The surface topology of virus filaments on respiratory syncytial virus (RSV)-infected cells was examined using field emission gun-scanning electron microscopy (FEG-SEM) and atomic force microscopy (AFM). FEG-SEM analysis of the surface of RSV-infected cells labelled with an anti-G protein antibody revealed the presence of virus filaments and clusters of the G protein distributed intermittently along their surface. RSV-infected cells thinly coated with chromium were imaged using FEG-SEM and revealed a distinct structured surface topology consisting of closely packed surface domains. The G protein clusters were only associated within a subset of these domains which suggested that this structured topology was mainly derived from the host cell, and the presence of the cell glycocalyx that coats the virus filaments was further suggested. Imaging of RSV-infected cells using AFM was undertaken as a different but complementary approach to the FEG-SEM analysis. Imaging using AFM revealed a similar structured surface topology on the virus filaments to that observed in the FEG-SEM analysis, indicating the consistency in the appearance of the virus surface topology using these different methods. Collectively, this study provides the first detailed imaging of the surface topology of the virus filaments as they form on RSV-infected cells. The imaging data is consistent with the envelopment of the virus filaments by the glycocalyx and highlights the complexity of the spatial organisation within the viral envelope.

microbiology↗

bioRxiv2024

Theca cell mechanics and tissue pressure regulate mammalian ovarian folliculogenesis

The maturation of functional eggs within the ovaries is essential for successful reproduction and organismal functions in mammals. Yet, despite its biological and clinical importance, the underlying mechanisms regulating folliculogenesis remain enigmatic. Here, we report a novel role of the surface-anchoring theca cells (TCs) in regulating follicle growth through mechanical signalling. Direct mechanical measurements reveal that these TCs are highly contractile and exert compressive stress to the follicular interior, potentially through active assembly of fibronectin scaffold around the follicles. Abolishing TC contractility disrupts fibronectin assembly, increases follicle size, and decreases intrafollicular pressure and viscosity. We further reveal that the granulosa cells (GCs) within the follicles exhibit spatial patterns of YAP signalling and proliferation, which appear to be decoupled. Transient manipulation of tissue pressure through bulk follicle compression, laser ablation or pharmacological perturbation of TC contractility leads to changes in GC YAP signalling, proliferation, and oocyte-GC communications, while long term abrogation of TC contractility leads to impaired follicle growth. Altogether, our study unveils the unique role of TC-mediated tissue pressure in ensuring robust mammalian ovarian folliculogenesis.

developmental biology↗