Synergetic impacts of turbulence and fishing reduce ocean biomass

A universal scaling relationship exists between organism abundance and body size1,2. Within ocean habitats this relationship deviates from that generally observed in terrestrial systems2–4, where marine macro-fauna display steeper size-abundance scaling than expected. This is indicative of a fundamental shift in food-web organization, yet a conclusive mechanism for this pattern has remained elusive. We demonstrate that while fishing has partially contributed to the reduced abundance of larger organisms, a larger effect comes from ocean turbulence: the energetic cost of movement within a turbulent environment induces additional biomass losses among the nekton. These results identify turbulence as a novel mechanism governing the marine size-abundance distribution, highlighting the complex interplay of biophysical forces that must be considered alongside anthropogenic impacts in processes governing marine ecosystems.

Genomic, epigenomic, and biophysical cues controlling the emergence of the lung alveolus

The lung alveolus is the functional unit of the respiratory system required for gas exchange. During the transition to air breathing at birth, biophysical forces are thought to shape the emerging tissue niche. However, the intercellular signaling that drives these processes remains poorly understood. Applying a multimodal approach, we identified alveolar type 1 (AT1) epithelial cells as a distinct signaling hub. Lineage tracing demonstrates that AT1 progenitors align with receptive, force-exerting myofibroblasts in a spatial and temporal manner. Through single-cell chromatin accessibility and pathway expression (SCAPE) analysis, we demonstrate that AT1-restricted ligands are required for myofibroblasts and alveolar formation. These studies show that the alignment of cell fates, mediated by biophysical and AT1-derived paracrine signals, drives the extensive tissue remodeling required for postnatal respiration.

Bacterial nanotubes as a manifestation of cell death

Bacterial nanotubes are membranous structures that have been reported to function as conduits between cells to exchange DNA, proteins, and nutrients. Here, we investigate the morphology and formation of bacterial nanotubes using Bacillus subtilis. We show that nanotube formation is associated with stress conditions, and is highly sensitive to the cells’ genetic background, growth phase, and sample preparation methods. Remarkably, nanotubes appear to be extruded exclusively from dying cells, likely as a result of biophysical forces. Their emergence is extremely fast, occurring within seconds by cannibalizing the cell membrane. Subsequent experiments reveal that cell-to-cell transfer of non-conjugative plasmids depends strictly on the competence system of the cell, and not on nanotube formation. Our study thus supports the notion that bacterial nanotubes are a post mortem phenomenon involved in cell disintegration, and are unlikely to be involved in cytoplasmic content exchange between live cells.

Biophysical forces rewire cell metabolism to guide microtubule-dependent cell mechanics

Mechanical signals regulate cell shape and influence cell metabolism and behavior. Cells withstand external forces by adjusting the stiffness of its cytoskeleton. Microtubules (MTs) act as compression-bearing elements in response to mechanical cues. Therefore, MT dynamics affect cell mechanics. Yet, how mechanical loads control MT dynamics to adjust cell mechanics to its locally constrained environment has remained unclear. Here, we show that mechanical forces rewire glutamine metabolism to promote MT glutamylation and force cell mechanics, thereby modulating mechanodependent cell functions. Pharmacologic inhibition of glutamine metabolism decreased MT glutamylation and affected their mechanical stabilization. Similarly, depletion of the tubulin glutamylase TTLL4 or overexpression of tubulin mutants lacking glutamylation site(s) increased MT dynamics, cell compliance and contractility, and thereby impacted cell spreading, proliferation and migration. Together our results indicate that mechanical cues sustain cell mechanics through glutaminolysis-dependent MT glutamylation, linking cell metabolism to MT dynamics and cell mechanics. Furthermore, our results decipher part of the enigmatic tubulin code that coordinates the fine tunable properties of MT mechanics, allowing cells to adjust the stiffness of their cytoskeleton to the mechanical loads of their environment.

Increased stiffness of the tumor microenvironment in colon cancer stimulates cancer associated fibroblast-mediated prometastatic activin A signaling

Colorectal cancer (CRC) is the second deadliest cancer in the US due to its propensity to metastasize. Stromal cells and especially cancer-associated fibroblasts (CAF) play a critical biophysical role in cancer progression, but the precise pro-metastatic mechanisms are not clear. Activin A, a TGF-β family member, is a strong pro-metastatic cytokine in the context of CRC. Here, we assessed the link between biophysical forces and pro-metastatic signaling by testing the hypothesis that CAF-generated mechanical forces lead to activin A release and associated downstream effects. Consistent with our hypothesis, we first determined that stromal activin A secretion increased with increasing substrate stiffness. Then we found that stromally-secreted activin A induced ligand-dependent CRC epithelial cell migration and epithelial to mesenchymal transition (EMT). In addition, serum activin A levels are significantly increased in metastatic (stage IV) CRC patients (1.558 ng/ml versus 0.4179 ng/ml, p < 0.05). We propose that increased tumor microenvironment stiffness leads to stromal cell-mediated TGF-β family signaling relying on the induction and utilization of activin A signaling.

Insights into the biophysical forces between proteins involved in elastic fiber assembly

The adhesive forces between various proteins involved in elastic fiber assembly were quantified using an atomic force microscope.

Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates lung injury during mechanical ventilation

ABSTRACTDuring mechanical ventilation, injurious biophysical forces exacerbate lung injury. These forces disrupt alveolar capillary barrier integrity, trigger proinflammatory mediator release, and differentially regulate genes and non-coding oligonucleotides such as microRNAs. In this study, we identify miR-146a as a mechanosensitive microRNA in alveolar macrophages that has therapeutic potential to mitigate lung injury during mechanical ventilation. We used humanized in-vitro systems, mouse models, and biospecimens from mechanically ventilated patients to elucidate the expression dynamics of miR-146a that might be required to decrease lung injury during mechanical ventilation. We found that the endogenous increase in miR-146a following injurious was relatively modest and not sufficient to prevent lung injury. However, when miR-146a was highly overexpressed using a nanoparticle-based delivery platform in vivo, it was sufficient to prevent lung injury. These data indicate that the endogenous increase in microRNA-146a during MV is a compensatory response that only partially limits VILI and that nanoparticle delivery approaches that significantly over-express microRNA-146a in AMs is an effective strategy for mitigating VILI.

Interspecies interactions in bacterial colonies are determined by physiological traits and the environment

Interspecies interactions in bacterial biofilms have important impacts on the composition and function of communities in natural and engineered systems. To investigate these interactions, synthetic communities provide experimentally tractable systems. Agar-surface colonies are similar to biofilms and have been used for investigating the eco-evolutionary and biophysical forces that determine community composition and spatial distribution of bacteria. Prior work has focused on intraspecies interactions, using differently fluorescent tagged but identical or genetically modified strains of the same species. Here, we investigated how physiological differences determine the community composition and spatial distribution in synthetic communities of Pseudomonas aeruginosa, Pseudomonas protegens and Klebsiella pneumoniae. Using quantitative microscopic imaging, we found that interspecies interactions in multispecies colonies are influenced by type IV pilus mediated motility, extracellular matrix secretion, environmental parameters and the specific species involved. These results indicate that the patterns observable in mixed species colonies can be used to understand the mechanisms that drive interspecies interactions, which are dependent on the interplay between specific species’ physiology and environmental conditions.