Biology subjects

Wieser, S.

Publications and source records attributed to Wieser, S..

8 recordsLinked to original sources

bioRxiv2025

De novo E-cadherin/catenin complex formation controls basal epithelial mechanics and force transmission for apoptotic cell clearance

Beyond serving as cohesive barriers, epithelia clear apoptotic cells to regulate development, homeostasis and inflammation. How epithelial cells remodel their shape during phagocytosis while preserving tissue integrity, and the role of adhesion receptors in this process, remain unclear. Using live in vivo imaging of phagocyte-target interactions in zebrafish (Danio rerio) embryos, we show that basal and apical epithelial domains are mechanically decoupled, enabling engulfment without disrupting tissue cohesion. We identify a dynamic assembly of E-cadherin/catenin complexes at the basal epithelial surface in contact with apoptotic cells. Targeted perturbations reveal two critical functions of de novo E-cadherin/catenin complex formation at the phagocytic synapse: -catenin acts as a physical linker transmitting actin-generated forces required for engulfment, while p120-catenin restrains Myosin II activity, enabling efficient clearance. We further demonstrate the conservation of E-cadherin-dependent apoptotic cell clearance in the mouse trophectoderm. These findings reveal that the E-cadherin/catenin complex is repurposed at the phagocytic synapse as a mechano-regulator of epithelial efferocytosis beyond its canonical role in tissue cohesion.

cell biology↗

bioRxiv2025

Targeting RhoA activity rejuvenates aged hematopoietic stem cells

Biomechanical alterations contribute to the decreased regenerative capacity of hematopoietic stem cells (HSCs) upon aging. RhoA is a key regulator of mechano-signaling but its role for mechanotransduction in stem cell aging has not been investigated yet. Here, we show that murine HSCs respond to increased nuclear envelope (NE) tension by inducing NE translocation of P-cPLA2, which cell intrinsically activates RhoA. Interestingly, aged HSCs experience physiologically higher intrinsic NE tension, associated with increased NE P-cPLA2 and RhoA activity. Reducing RhoA activity lowers NE tension in aged HSCs. Feature image analysis of HSC nuclei reveals that chromatin remodeling is associated to RhoA inhibition, which includes the restoration of youthful levels of the heterochromatin marker H3K9me2 and a decrease in chromatin accessibility and transcription at retrotransposons. Eventually, we demonstrate that RhoA inhibition upregulates Klf4 expression and transcriptional activity, improving aged HSCs regenerative capacity and lympho/myeloid skewing in vivo. Overall, our data support that an intrinsic mechano-signaling axis dependent on RhoA can be pharmacologically targeted to rejuvenate stem cell function upon aging.

cell biology↗

bioRxiv2022

Advected percolation in the actomyosin cortex drives amoeboid cell motility

Spontaneous locomotion is a common feature of most metazoan cells, generally attributed to the fundamental properties of the actomyosin network. This force-producing machinery has been studied down to the most minute molecular details, especially in lamellipodium-driven migration. Nevertheless, how actomyosin networks work inside contraction-driven amoeboid cells still lacks unifying principles. Here, using stable motile blebs as a model amoeboid motile system, we image the dynamics of the actin cortex at the single filament level and reveal the co-existence of three phases of the actin network with distinct rheological properties. Physical modelling shows that these three phases organize spontaneously due to a rigidity percolation transition combined with an active advection of the percolated network. This spontaneous spatial organization of the mechanical properties of the actin network, which we propose to call advected percolation, constitutes a minimal and generic locomotion mechanism. It explains, down to the single actin filament level and up to the scale of the entire cell, how amoeboid cells can propel efficiently through complex 3D environments, a feature shared by immune and cancer cells.

biophysics↗

bioRxiv2022

A rigidity phase transition of Stomatin condensates governs a switch from transport to mechanotransduction

A large body of work suggests that biomolecular condensates ensuing from liquid-liquid phase separation mature into various material states. How this aging process is controlled and if the naive and mature phases can have differential functions is currently unknown. Using Caenorhabditis elegans as a model, we show that MEC-2 Stomatin undergoes a rigidity phase transition during maturation from fluid to viscoelastic, glass-like condensates that facilitate either transport or mechanotransduction. This switch is promoted by the SH3 domain of UNC-89/Titin/Obscurin through a direct interaction with MEC-2 and suggests a physiological role for a percolation transition in force transmission during body wall touch. Together, our data demonstrate a novel function for rigidity maturation during mechanotransduction and a previously unidentified role for Titin homologs in neurons.

cell biology↗

bioRxiv2019

The nucleus measures shape deformation for cellular proprioception and regulates adaptive morphodynamics

The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within their local environment remains largely unknown. Here we show that the nucleus, the biggest cellular organelle, functions as a non-dissipative cellular shape deformation gauge that enables cells to continuously measure shape variations on the time scale of seconds. Inner nuclear membrane unfolding together with the relative spatial intracellular positioning of the nucleus provides physical information on the amplitude and type of cellular shape deformation. This adaptively activates a calcium-dependent mechano-transduction pathway, controlling the level of actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behaviour to their microenvironment. One Sentence SummaryThe nucleus functions as an active deformation sensor that enables cells to adapt their behavior to the tissue microenvironment.

cell biology↗

bioRxiv2019

Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning

Neurons are among the most highly polarized cell types. They possess structurally and functionally different processes, axon and dendrites, to mediate information flow through the nervous system. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is little understood.\n\nUsing the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cell cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.

cell biology↗

bioRxiv2019

A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs

Through the asymmetric distribution of mRNAs cells spatially regulate gene expression to create cyto-plasmic domains with specialized functions. In mammalian neurons, mRNA localization is required for essential processes as cell polarization, migration and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. Here, we report the first reconstitution of a mammalian mRNA transport system revealing that the tumour suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localised {beta}-actin and {beta}2B-tubulin mRNAs which are linked to a heterotrimeric kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2 and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal for the first time a minimal set of proteins capable of driving kinesin-based, mammalian mRNA transport.

biochemistry↗

bioRxiv2018

Habitat-Net: Segmentation of habitat images using deep learning

Understanding environmental factors that influence forest health, as well as the occurrence and abundance of wildlife, is a central topic in forestry and ecology. However, the manual processing of field habitat data is time-consuming and months are often needed to progress from data collection to data interpretation. Computer-assisted tools, such as deep-learning applications can significantly shortening the time to process the data while maintaining a high level of accuracy. Here, we propose Habitat-Net: a novel method based on Convolutional Neural Networks (CNN) to segment habitat images of tropical rainforests. Habitat-Net takes color images as input and after multiple layers of convolution and deconvolution, produces a binary segmentation of the input image. We worked on two different types of habitat datasets that are widely used in ecological studies to characterize the forest conditions: canopy closure and understory vegetation. We trained the model with 800 canopy images and 700 understory images separately and then used 149 canopy and 172 understory images to test the performance of Habitat-Net. We compared the performance of Habitat-Net with a simple threshold based method, a manual processing by a second researcher and a CNN approach called U-Net upon which Habitat-Net is based. Habitat-Net, U-Net and simple thresholding reduced total processing time to milliseconds per image, compared to 45 seconds per image for manual processing. However, the higher mean Dice coefficient of Habitat-Net (0.94 for canopy and 0.95 for understory) indicates that accuracy of Habitat-Net is higher than that of both the simple thresholding (0.64, 0.83) and U-Net (0.89, 0.94). Habitat-Net will be of great relevance for ecologists and foresters, who need to monitor changes in their forest structures. The automated workflow not only reduces the time, it also standardizes the analytical pipeline and, thus, reduces the degree of uncertainty that would be introduced by manual processing of images by different people (either over time or between study sites). Furthermore, it provides the opportunity to collect and process more images from the field, which might increase the accuracy of the method. Although datasets from other habitats might need an annotated dataset to first train the model, the overall time required to process habitat photos will be reduced, particularly for large projects.

ecology↗