Biology subjects

Banerji, R.

Publications and source records attributed to Banerji, R..

5 recordsLinked to original sources

bioRxiv2025

Mosaic pattern: lung functional heterogeneity at the alveolus level

Inhaled particles carrying pathogens, pollutants (e.g., microplastics, smoke), therapeutics, and diagnostics are increasingly relevant to public health, yet real-time tracking of aerosol transport in functional alveoli remains challenging. Here, we used the recently developed crystal ribcage to investigate aerosol transport in ex vivo lungs during active ventilation, obtaining the first real-time observations of single aerosol droplet transport and deposition in functional alveoli. We discovered deterministic heterogeneity at both intra- and inter-alveolar levels, with aerosol distribution forming a characteristic "mosaic" pattern in which only specific alveolar clusters received particles. The pattern was consistently formed in vivo during spontaneous breathing and ex vivo using both positive- and negative-pressure ventilation. This pattern was also consistent across a range of aerosols, including small molecules, nanobodies, nanoparticles, microplastics, therapeutics, and pathogens. Additionally, the pattern was observed in murine, porcine, and human lungs, and evolved from birth through aging in mice. The post-deposition stability of the pattern depended on particle type and lung age, lasting from a few minutes for small molecular weight particles to multiple days for cell-binding particles. These alveolar-level heterogeneities may uncover previously unrecognized biological and immunological heterogeneities associated with the mosaic pattern, including its role in postnatal lung development, susceptibility to inhaled airborne hazards such as pollutants and infectious agents, and early pathogenesis and response to inhaled therapeutics in respiratory diseases such as pneumonia, COPD, asthma, and lung cancer.

bioengineering↗

bioRxiv2025

Micromechanics of lung capillaries across mouse lifespan and in positive- vs negative-pressure ventilation

The lung undergoes continuous remodeling throughout normal development and aging, including changes to alveolar and capillary structure and function. While histological methods allow static analysis of these age-related changes, characterizing the changes that occur in response to mechanical stimuli remains difficult, particularly over a dynamic, physiologically relevant range in a functioning lung. Alveolar and capillary distension - the change in diameter of alveoli and capillaries, respectively, in response to pressure changes - is one such process, where dynamically controlling and monitoring the diameter of the same capillary or alveolus is essential to infer its mechanical properties. We overcome these limitations by utilizing the recently developed crystal ribcage to image the alveoli and vasculature of a functional mouse lung across the lifespan in postnatal (6-7 days), young adult (12-18 weeks), and aged (20+ months) mice. Using a range of biologically relevant vascular (0-15 cmH2O) and transpulmonary (3-12 cmH2O) pressures, we directly quantify vascular and alveolar distention in the functional lung as we precisely adjust pulmonary pressures. Our results show differences in age-related alveolar and vascular distensibility: when we increase transpulmonary alveolar or vascular pressure, vessels in postnatal lungs expand less and undergo less radial and axial strain, under each respective pressure type, suggesting stiffer capillaries than in older lungs. However, while vessels in young adult and aged lungs respond similarly to variations in vascular pressure, differences in elasticity start to emerge at the alveolar scale in response to transpulmonary alveolar pressure changes. Our results further indicate that differing effects of ventilation mode (i.e., positive vs negative) present themselves at the capillary level, with vessels under positive pressure undergoing more compression than when under negative-pressure conditions. These findings contribute both to the understanding of the functional changes that occur within the lung across the lifespan, as well as to the debate of ventilation effects on lung microphysiology.

physiology↗

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↗

bioRxiv2022

Probing lung function at high spatiotemporal resolution using a novel crystal ribcage

Understanding the dynamic pathogenesis and treatment response in pulmonary diseases requires probing the lung at cellular resolution in real-time. Despite recent progress in intravital imaging, optical imaging of the lung during active respiration and circulation has remained challenging. Here, we introduce the crystal ribcage: a transparent ribcage that (i) allows truly multiscale optical imaging of the lung in health and disease from whole-organ to single cell, (ii) enables the modulation of lung biophysics and immunity through intravascular, intrapulmonary, intraparenchymal, and optogenetic interventions, and (iii) preserves the 3-D architecture, air-liquid interface, cellular diversity, and respiratory-circulatory functions of the lung. Utilizing these unprecedented capabilities on murine models of primary and metastatic lung tumors, respiratory infection, pulmonary fibrosis, emphysema, and acute lung injury we probed how disease progression remodels the respiratory-circulatory functions at the single alveolus and capillary levels. In cancer, we identified the earliest stage of tumorigenesis that compromises alveolar and capillary functions, a key state with consequences on tumor progression and treatment response. In pneumonia, we mapped mutual links between the recruited immune cells and the alveolar-capillary functions. We found that neutrophil migration is strongly and reversibly responsive to vascular pressure with implications for understanding of how lung physiology, altered by disease and anatomical location, affects immune cell activities. The crystal ribcage and its broad applications presented here will facilitate further studies of real-time remodeling of the alveoli and capillaries during pathogenesis of nearly any pulmonary disease, leading to the identification of new targets for treatment strategies.

bioengineering↗

bioRxiv2021

Structure-Function Relationships of the Vertebral Endplate

BackgroundAlthough deformation and fracture of the vertebral endplate have been implicated in spinal conditions such as vertebral fracture and disc degeneration, few biomechanical studies of this structure are available. The goal of this study was to quantify the mechanical behavior of the vertebral endplate. MethodsEight-five rectangular specimens were dissected from the superior and/or inferior central endplates of human lumbar spine segments L1-L4. Micro-computed tomography (CT) imaging, four-point-bend testing, and ashing were performed to quantify the apparent elastic modulus and yield stress (modulus and yield stress, respectively, of the porous vertebral endplate), tissue yield stress (yield stress of the tissue of the vertebral endplate, excluding pores), ultimate strain, fracture strain, bone volume fraction (BV/TV), bone mineral density (BMD), and various measures of tissue density and composition (tissue mineral density, ash fraction, and ash density). Regression was used to assess the dependence of mechanical properties on density and composition. ResultsWide variations in elastic and failure properties, and in density and tissue composition, were observed. BMD and BV/TV were good predictors of many of the apparent-level mechanical properties, including modulus, yield stress, and in the case of the inferior vertebral endplate, failure strains. Similar values of the mechanical properties were noted between superior and inferior vertebral endplates. In contrast to the dependence of apparent stiffness and strength on BMD and BV/TV, none of the mechanical properties depended on any of the tissue-level density measurements. ConclusionThe dependence of many of the mechanical properties of the vertebral endplate on BV/TV and BMD suggests possibilities for non-invasive assessment of how this region of the spine behaves during habitual and injurious loading. Further study of the non-mineral components of the endplate tissue is required to understand how the composition of this tissue may influence the overall mechanical behavior of the vertebral endplate.

bioengineering↗