Biology subjects

Nia, H.

Publications and source records attributed to Nia, H..

3 recordsLinked to original sources

bioRxiv2026

Neutrophil migration in the lung is altered by alveolar collapse and stretch

RationaleHeterogeneous alveolar collapse is prevalent in inflammatory lung conditions such as chronic obstructive pulmonary disease, acute respiratory distress syndrome, and pneumonia. Although neutrophil-released proteases contribute to the tissue remodeling that leads to alveolar collapse, how this altered mechanical environment in turn affects neutrophil migration remains largely unexplored. ObjectivesIn this study, we investigate how alveolar collapse and stretch influence neutrophil migration and identify the mechanical and biochemical factors that govern regional migration differences. MethodsWe developed a novel precision-cut lung slice platform that generates collapsed vs non-collapsed regions within the same slice. Neutrophils in both regions were longitudinally imaged for up to 5 hours to quantify motility behavior. Migration mechanisms were probed using migration-related inhibitors, collagenase, and cigarette smoke extract. A crystal ribcage system, which preserves intact alveolar shape and the air-liquid interface, was also used to assess the effects of ventilation on neutrophil migration. ResultsNeutrophil migration was faster in the collapsed region compared to not-collapsed regions. This regional difference was eliminated by Rho-associated protein kinase (ROCK) inhibition, which selectively increased migration speed in the non-collapsed region. The regional difference persisted with the addition of collagenase and cigarette smoke extract, both of which significantly increased the migration speed in both regions. In the crystal ribcage, the preserved air-liquid interface and ventilation together enhanced neutrophil migration compared with a collapsed lung. ConclusionsAlveolar collapse and stretch facilitate neutrophil migration, indicating the role of localized tissue remodeling in driving neutrophil activity and further disease progression.

bioengineering↗

bioRxiv2024

Dispersion indices for universal quantification of fluorescently-labelled subcellular structure spatial distributions

Image analysis of subcellular structures and biological processes relies on specific, context-dependent pipelines, which are labor-intensive, constrained by the intricacies of the specific biological system, and inaccessible to broader applications. Here we introduce the application of dispersion indices, a statistical tool traditionally employed by economists, to analyze the spatial distribution and heterogeneity of subcellular structures. This computationally efficient high-throughput approach, termed GRID (Generalized Readout of Image Dispersion), is highly generalizable, compatible with open-source image analysis software, and adaptable to diverse biological scenarios. GRID readily quantifies diverse structures and processes to include autophagic puncta, mitochondrial clustering, and microtubule dynamics. Further, GRID is versatile, applicable to both 2D cell cultures and 3D multicellular organoids, and suitable for high-throughput screening and performance metric measurements, such as half-maximal effective concentration (EC50) values. The approach enables mechanistic analysis of critical subcellular structure processes of relevance for diseases ranging from metabolic and neuronal diseases to cancer as well as a first-pass screening method for identifying biologically active agents for drug discovery. Statement of SignificanceCurrent methods for image analysis in microscopy are tailored to specific biological contexts, which creates challenges in implementation and efficiency for researchers studying a diverse range of subcellular processes. Our application of dispersion indices, traditionally used in economics, offers a universal framework for high throughput quantification of biological structures, enabling easier and more consistent analysis across various biological contexts. By transforming pixel intensity and count into meaningful statistical measures, our method simplifies the quantification of subcellular structures such as autophagic puncta, microtubule dynamics, and mitochondrial clustering. This approach accelerates the quantitative analysis of sub-cellular processes in disease as well as imaged-based drug discovery. Classification: Bioengineering, Cell Biology, Applied Biological Sciences

cell biology↗

bioRxiv2023

Alteration of mechanical stresses in the murine brain by age and hemorrhagic stroke

Residual mechanical stresses in tissues arise during rapid differential growth or remodeling such as in morphogenesis and cancer. These residual stresses, also known as solid stresses, are distinct from fluid pressures and dissipate in most healthy adult organs as the rate of growth decreases. However, studies have shown that residual stresses remain substantially high even in mature, healthy brains. The genesis and consequences of these mechanical stresses in a healthy brain, and in aging and disease remain to be explored. Here, we utilized and validated our previously developed method to map residual mechanical stresses in the brains of mice in three different age groups: 5-7 days, 8-12 weeks, and 22 months old. We found that residual solid stress increases rapidly from 5-7 days to 8-12 weeks in mice, and remains high even in mature 22-month-old mice brains. Three-dimensional mapping of the residual stresses revealed an increasing trend from anterior to posterior in coronal sections of the brain. Since the brain is rich in negatively charged hyaluronic acid, we evaluated the contribution of charged extracellular matrix (ECM) constituents in maintaining solid stress levels. We found that lower ionic strength leads to elevated solid stresses, a finding consistent with the unshielding effect of low ionic strength and the subsequent expansion of charged ECM components. Lastly, we demonstrated that hemorrhagic stroke, accompanied by loss of cellular density, resulted in decreased levels of residual stress in the murine brain. Our findings contribute to a better understanding of the spatiotemporal alteration of residual solid stresses in healthy and diseased brains, a crucial step toward uncovering the biological and immunological consequences of this understudied mechanical phenotype in the brain. Significance StatementWhile emerging evidence highlights the importance of solid stresses in embryogenesis and tumor growth, the genesis and consequences of residual solid stresses in the adult normal brain remain poorly understood. Understanding the spatiotemporal distribution and alteration of the residual solid stresses as the brain ages and is impacted by neuropathologies, such as a stroke, will elucidate the biological and immunological consequences of maintaining these stresses. This study suggests solid stress could serve as a potential biomarker in aging and diseases associated to the brain.

biophysics↗