Biology subjects

Roeder, J.

Publications and source records attributed to Roeder, J..

6 recordsLinked to original sources

bioRxiv2026

Mechanochemical synchronization of force oscillations in connective tissue models

Cells in a tissue coordinate their behavior collectively by mechanical and chemical feedback with their surroundings. To study how such feedback mechanisms interact, we embed multicellular spheroids from mouse and primary human fibroblasts of different origin in 3D collagen matrices. Immediately after embedding, spheroids apply steadily increasing, radially symmetric, inward-directed forces to the surrounding matrix. Typically, within a few hours, collective force oscillations emerge with an average time interval of {approx}30 min. Similar force oscillations also arise in engineered, parallel-aligned microtissues attached to flexible pillars. Force oscillations propagate between neighboring cells as a mechanical wave, accompanied by calcium waves that travel at comparable speeds of several hundred m/min. Blocking gap junctions or mechanosensitive Piezo1 channels impairs these oscillations, indicating that calcium signaling contributes to their propagation. Their amplitude and frequency are regulated by integrin-mediated feedback in actin-rich protrusions and by ERK signaling, which also controls collective invasion into the surrounding matrix. Neighboring spheroids mechanically synchronize their force oscillations in phase and frequency over distances of up to {approx}2 mm without direct contact. Together, our results show that oscillatory mechanochemical feedback enables multicellular systems to coordinate force generation and invasive migration across cellular and millimeter length scales in 3D matrices.

biophysics↗

bioRxiv2025

Longitudinal in vivo MR elastography reveals whole-liver viscoelastic involvement in a murine model of hepatocellular carcinoma

Cancer cells actively shape their microenvironment and adapt the physical and biomechanical properties of the host tissue. However, for organs like the liver, especially in vivo, it remains unclear at what rate and spatial extent macroscopic viscoelastic properties change during formation of a cancer-permissive environment. Using clinical multifrequency magnetic resonance elastography (MRE) in a mouse model of hepatocellular carcinoma (HCC), we identified surprisingly early and large-scale viscoelasticity changes leading to whole-liver biomechanical involvement stretching far beyond the local cancer microenvironment. Widespread liver softening began two weeks after HCC inoculation, followed by a decrease in tissue viscosity and fluidity two weeks later, preceding any macroscopic evidence of local tumor growth. In contrast, local lesions with stiff-rigid biomechanical properties were not detectable by standard MRI and MRE until five to six weeks post-injection. Furthermore, tumor viscoelasticity correlated with that of the host liver, also suggesting a possible widespread adaptation of the biomechanical properties beyond the tumor margins and its local niche during early liver colonization. The observed large-scale viscoelastic signature, detectable just two weeks after tumor cells injection, could serve as a non-invasive imaging biomarker to inform physicians about tumor niche formation and liver cancer progression long before any macroscopic manifestation of solid tumors.

biophysics↗

bioRxiv2024

Two temperature-responsive RNAs act in concert: The small RNA CyaR and the mRNA ompX

Bacterial pathogens, such as in Yersinia pseudotuberculosis, encounter temperature fluctuations during host infection and upon return to the environment. These temperature shifts impact RNA structures globally. While previous transcriptome-wide studies have focused on RNA thermometers in the 5-untranslated region of virulence-related mRNAs, our investigation revealed temperature-driven structural rearrangements in the small RNA (sRNA) CyaR. At 25{degrees}C, CyaR primarily adopts a conformation that occludes its seed region, but transitions to a liberated state at 37{degrees}C. By RNA-sequencing and in-line probing experiments, we identified the Shine-Dalgarno sequence of ompX as a direct target of CyaR. Interestingly, the ompX transcript itself exhibits RNA thermometer-like properties, facilitating CyaR base pairing at elevated temperatures. This interaction impedes ribosome binding to ompX and accelerates degradation of the ompX transcript. Furthermore, we observed induced proteolytic turnover of the OmpX protein at higher temperatures. Collectively, our study uncovered multi-layered posttranscriptional mechanisms governing ompX expression, resulting in lower OmpX levels at 37{degrees}C compared to 25{degrees}C. We propose that CyaR remains mostly passive at 25{degrees}C but becomes primed to repress ompX at 37{degrees}C, thereby expediting outer membrane remodelling in anticipation of pathogenesis.

microbiology↗

bioRxiv2021

Characterization of changes in the hemagglutinin that accompanied the emergence of H3N2/1968 pandemic influenza viruses

The hemagglutinin (HA) of A/H3N2 pandemic influenza viruses (IAVs) of 1968 differed from its inferred avian precursor by eight amino acid substitutions. To determine their phenotypic effects, we studied recombinant variants of A/Hong Kong/1/1968 virus containing either human-type or avian-type amino acids in the corresponding positions of HA. The precursor HA displayed receptor binding profile and high conformational stability typical for duck IAVs. Substitutions Q226L and G228S, in addition to their known effects on receptor specificity and replication, marginally decreased HA stability. Substitutions R62I, D63N, D81N and N193S reduced HA binding avidity. Substitutions R62I, D63N, D81N and A144G promoted virus replication in human airway epithelial cultures. Analysis of HA sequences revealed that substitutions D63N and D81N accompanied by the addition of N-glycans represent common markers of avian H3 HA adaptation to mammals. Our results advance understanding of genotypic and phenotypic changes in IAV HA required for avian-to-human adaptation and pandemic emergence.

microbiology↗

bioRxiv2020

Comprehensive single cell analyses of the nutritional environment of intracellular Salmonella enterica

The facultative intracellular pathogen Salmonella enterica Typhimurium (STM) resides in a specific membrane-bound compartment termed the Salmonella-containing vacuole (SCV). STM is able to obtain all nutrients required for rapid proliferation, although being separated from direct access to host cell metabolites. The formation of specific tubular membrane compartment, called Salmonella-induced filaments (SIFs) are known to provides bacterial nutrition by giving STM access to endocytosed material and enabling proliferation. Additionally, STM expresses a range of nutrient uptake system for growth in nutrient limited environments to overcome the nutrition depletion inside the host. By utilizing dual fluorescence reporters, we shed light on the nutritional environment of intracellular STM in various host cells and distinct intracellular niches. We showed that STM uses nutrients of the host cell and adapts uniquely to the different nutrient conditions. In addition, we provide further evidence for improved nutrient supply by SIF formation or presence in the cytosol of epithelial cells, and the correlation of nutrient supply to bacterial proliferation.

microbiology↗

bioRxiv2020

Single cell analyses reveal phosphate availability as critical factor for nutrition of Salmonella enterica within mammalian host cells

Salmonella enterica serovar Typhimurium (STM) is an invasive, facultative intracellular pathogen that resides in a specialized membrane-bound compartment termed Salmonella-containing vacuole (SCV). Essential for survival and proliferation in the SCV is Salmonella pathogenicity island II (SPI2) that encodes a type III secretion system (T3SS). The SPI2-T3SS and the effector translocation maintain SCV integrity and formation of specific tubular membrane compartments, called Salmonella-induced filaments (SIFs). The SCV/SIF continuum allows STM to bypass nutritional restriction in the intracellular environment by acquiring nutrients from the host cell. Phosphate is one of the most abundant elements in living organisms and in STM, inorganic phosphate (Pi) homeostasis is mediated by the two-component regulatory system PhoBR, resulting in expression of the high affinity phosphate transporter pstSCAB-phoU. Using fluorescent protein reporters, we investigate Pi availability for STM at single cell level over time within the intracellular habitats of different host cells. We observed that the pstSCAB-phoU encoded phosphate uptake system is essential for intracellular replication of STM because there is a Pi ion concentration less 10 M within the SCV. Additionally, the demand and consumption of Pi correlates with intracellular proliferation of STM and we identify a dependency of SPI2 activity and Pi starvation.

microbiology↗