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Mathijssen, A. J.

Publications and source records attributed to Mathijssen, A. J..

4 recordsLinked to original sources

A Two-Component Regulatory System Mediates Quorum Sensing-Dependent Morphology and Motility Transitions in the Archaeon Haloferax volcanii

Quorum sensing (QS) enables microorganisms--including bacteria, eukaryotes, and viruses--to coordinate collective behaviors in response to population density. Despite their ecological and evolutionary significance, QS mechanisms in Archaea remain poorly characterized. The halophilic archaeon Haloferax volcanii provides a model for archaeal QS, transitioning from motile rods to non-motile disks in a density-dependent response to a secreted disk-forming signal (DFS). To identify components of the DFS regulatory network, we screened for spontaneous mutants that retained motility in DFS-containing soft-agar medium. One candidate, HVO_1357, encodes a predicted response regulator located adjacent to a histidine kinase (HVO_1356) and a second response regulator (HVO_1358), consistent with an extended two-component regulatory system (TCS). Based on our results, these genes encode quorum-sensing associated regulators (Qar), therefore, we propose rename them qarA (HVO_1357), qarB (HVO_1356), and qarC (HVO_1358). Deletion of qarA enabled cells to swim on DFS-containing soft-agar plates and conferred hypermotility on standard soft-agar media; however, these phenotypes were not due to changes in motility-related parameters, but a reduced sensitivity to DFS for induction of the non-motile, disk-shaped state. In contrast, {Delta}qarB and {Delta}qarC strains were non-motile and exhibited premature disk formation during normal growth. Suppressor mutations that restored motility to {Delta}qarB and {Delta}qarC mapped exclusively to qarA, suggesting QarA is the central regulator of this system. Transcriptomic analyses revealed that qarA deletion leads to upregulation of genes involved in motility and rod-shape formation. Together, these findings reveal qarABC as a DFS-responsive regulatory module and represent the first TCS in archaea shown to control QS-dependent behavior. IMPORTANCEArchaea are ubiquitous and play key roles across diverse ecosystems--including human microbiomes--yet little is known about how they communicate with one another and with other organisms, or how these interactions shape their ecological impact. Such intercellular communication, including quorum sensing (QS), allows microorganisms to coordinate behaviors critical for survival, adaptation, and community organization. In this study, we identify the first archaeal two-component regulatory system that is involved in QS-dependent regulation, providing a foundation for understanding how organisms in this domain sense and respond to population cues. By revealing a previously unknown aspect of archaeal biology, this work represents an important step toward understanding how archaeal communication shapes both their physiology and their interactions within complex microbial communities.

microbiology↗

Metachronal wave coordination encodes multimodal swimming in ciliated unicellular predators

Motile cilia are slender cellular appendages, conserved across eukaryotes ranging from unicellular protists to humans, that beat to generate fluid flow. In most organisms, cilia form dense arrays of thousands of filaments that coordinate their motion into persistent, temporally synchronized patterns known as metachronal waves. Despite their ubiquity, the dynamics of these patterns and their role in tuning propulsion remain poorly understood. Here, we investigate how metachronal coordination shapes the navigation of Didinium nasutum, a highly agile unicellular predator with two circumferential ciliary bands. Using high-speed imaging of freely swimming cells, we capture and quantify the dynamics of metachronal wave coordination and track their evolution across different swimming states and transitions. Combining these measurements with a hydrodynamic model, we uncover how dynamic changes in coordination directly regulate propulsion and maneuverability. We show that stable metachronal waves support persistent directed swimming, local inhomogeneities in coordination give rise to curved trajectories, and global wave reversals accommodate rapid evasion-like reorientations. Our findings reveal that transitions between coordination modes allow Didinium to access a diverse swimming repertoire, highlighting dynamic ciliary patterning as a key mechanism to encode complex microscale navigation strategies. More broadly, they provide mechanistic insights into how metachronal coordination shapes fluid flows generated by dense ciliary arrays found in unicellular protists and airway epithelia alike, ultimately influencing swimming and transport in biological systems.

biophysics↗

Biphasic Mechanical Loading Disrupts Cytoskeletal Symmetry in 3D Architected Scaffolds

Cells in load-bearing tissues experience both solid deformation and interstitial fluid flow during physiological loading, but the mechanisms by which they integrate these biphasic mechanical signals remain poorly understood. Here, we develop a porous, nanoarchitected 3D scaffold that allows simultaneous delivery and control of matrix strain and fluid shear stress. We validated the platform through fatigue loading experiments and simulations of fluid-structure interactions. In static culture, osteoblast-like cells adopted shapes, cytoskeletal architectures, and focal adhesion patterns templated by scaffold geometry. Under cyclic compression, the combined influence of matrix deformation and induced fluid flow disrupted this alignment, producing disordered actin structures and reduced focal adhesion eccentricity. These changes emerged even under low-frequency loading, within the drained poroelastic regime, indicating a high sensitivity of cytoskeletal organization to fluid-solid coupling. Our findings establish a tractable and tunable platform to investigate how cells sense and respond to dynamic biphasic mechanical environments in 3D. Significance StatementCells in tissues such as bone experience mechanical inputs from both matrix deformation and interstitial fluid flow. However, existing in vitro systems often isolate one type of input or lack the ability to control both independently. We engineered a nanoarchitected 3D scaffold that delivers tunable biphasic mechanical inputs by combining structural compression and fluid flow. Without external loads, cells align their cytoskeleton and focal adhesions to the scaffold geometry. When subjected to dynamic loading, they transition to disordered morphologies and less mature focal adhesions, suggesting a transition to migratory states. These results highlight the sensitivity of cells to even subtle biphasic cues and provide a new platform to study how cells integrate multiple mechanical signals in 3D environments.

bioengineering↗

SARS-CoV-2 Delta Variant Remains Viable in Environmental Biofilms found in Meat Packaging Plants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus that directly infects human airway epithelial cells and caused the COVID-19 pandemic. At the start of the pandemic in 2020, meat-packaging plants saw a surge in SARS-CoV-2 cases, which forced many to temporarily close. To determine why SARS-CoV-2 appears to thrive specifically well in meat packaging plants, we used SARS-CoV-2 Delta variant and meat packaging plant drain samples to develop mixed-species biofilms on materials commonly found within meat packaging plants (stainless steel (SS), PVC, and ceramic tile). Our data provides evidence that SARS-CoV-2 Delta variant remained viable on all the surfaces tested with and without an environmental biofilm. We observed that SARS-CoV-2 Delta variant was able to remain infectious with each of the environmental biofilms, however, we detected a significant reduction in viability post-exposure to Plant B biofilm on SS, PVC, and on ceramic tile chips, and to Plant C biofilm on SS and PVC chips. The numbers of viable SARS-CoV-2 Delta viral particles was 1.81 - 4.57-fold high than the viral inoculum incubated with the Plant B and Plant C environmental biofilm on SS, and PVC chips. We did not detect a significant difference in viability when SARS-CoV-2 Delta variant was incubated with the biofilm obtained from Plant A on any of the materials tested and SARS-CoV-2 Delta variant had higher plaque numbers when inoculated with Plant C biofilm on tile chips, with a 2.75-fold difference compared to SARS-CoV-2 Delta variant on tile chips by itself. In addition, we detected an increase in the biofilm biovolume in response to SARS-CoV-2 Delta variant which is also a concern for food safety due to the potential for foodborne pathogens to respond likewise when they come into contact with the virus. These results indicate a complex virus-environmental biofilm interaction which correlates to the different bacteria found in each biofilm. Our results also indicate that there is the potential for biofilms to protect SARS-CoV-2 from disinfecting agents and remaining prevalent in meat packaging plants. With the highly infectious nature of some SARS-CoV-2 variants such as Delta, and more so with the Omicron variant, even a minimal amount of virus could have serious health implications for the spread and reoccurrence of SARS-CoV-2 outbreaks in meat packaging plants.

ecology↗