Dataset Information

Transport of ellipsoid fibers in oscillatory shear flows: Implications for aerosol deposition in deep airways.

ABSTRACT: It is widely acknowledged that inhaled fibers, e.g. air pollutants and anthropogenic particulate matter, hold the ability to deposit deep into the lungs reaching the distal pulmonary acinar airways as a result of their aerodynamic properties; these particles tend to align with the flow and thus stay longer airborne relative to their spherical counterpart, due to higher drag forces that resist sedimentation. Together with a high surface-to-volume ratio, such characteristics may render non-spherical particles, and fibers in particular, potentially attractive airborne carriers for drug delivery. Until present, however, our understanding of the dynamics of inhaled aerosols in the distal regions of the lungs has been mostly limited to spherical particles. In an effort to unravel the fate of non-spherical aerosols in the pulmonary depths, we explore through numerical simulations the kinematics of ellipsoid-shaped fibers in a toy model of a straight pipe as a first step towards understanding particle dynamics in more intricate acinar geometries. Transient translational and rotational motions of micron-sized ellipsoid particles are simulated as a function of aspect ratio (AR) for laminar oscillatory shear flows mimicking various inhalation maneuvers under the influence of aerodynamic (i.e. drag and lift) and gravitational forces. We quantify transport and deposition metrics for such fibers, including residence time and penetration depth, compared with spherical particles of equivalent mass. Our findings underscore how deposition depth is largely independent of AR under oscillatory conditions, in contrast with previous works where AR was found to influence deposition depth under steady inspiratory flow. Overall, our efforts underline the importance of modeling oscillatory breathing when predicting fiber deposition in the distal lungs, as they are inhaled and exhaled during a full inspiratory cycle. Such physical insight helps further explore the potential of fiber particles as attractive carriers for deep airway targeting.

SUBMITTER: Shachar-Berman L

PROVIDER: S-EPMC5810903 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Transport of ellipsoid fibers in oscillatory shear flows: Implications for aerosol deposition in deep airways.

Shachar-Berman Lihi L Ostrovski Yan Y De Rosis Alessandro A Kassinos Stavros S Sznitman Josué J

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 20170920

It is widely acknowledged that inhaled fibers, e.g. air pollutants and anthropogenic particulate matter, hold the ability to deposit deep into the lungs reaching the distal pulmonary acinar airways as a result of their aerodynamic properties; these particles tend to align with the flow and thus stay longer airborne relative to their spherical counterpart, due to higher drag forces that resist sedimentation. Together with a high surface-to-volume ratio, such characteristics may render non-spheric ...[more]

PMID: 28942008

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Project description:Atherosclerosis is a multifactorial disease that preferentially develops in specific regions in the arterial tree. This characteristic is mainly attributed to the unique pattern of hemodynamic shear stress in vivo. High laminar shear stress (LS) found in straight lumen exerts athero-protective effects. Low or oscillatory shear stress (OS) present in regions of lesser curvature and arterial bifurcations predisposes arterial intima to atherosclerosis. Shear stress-regulated endothelial function plays an important role in the process of atherosclerosis. Most in vitro research studies focusing on the molecular mechanisms of endothelial function are performed in endothelial cells (ECs) under cultured static (ST) condition. Some findings, however, are not recapitulated in subsequent translational studies, mostly likely due to the missing biomechanical milieu. Here, we profiled the whole transcriptome of primary human coronary arterial endothelial cells (HCAECs) under different shear stress conditions with RNA sequencing. Among 16,313 well-expressed genes, we detected 8,177 that were differentially expressed in OS vs. LS conditions and 9,369 in ST vs. LS conditions. Notably, only 1,618 were differentially expressed in OS vs. ST conditions. Hierarchical clustering of ECs demonstrated a strong similarity between ECs under OS and ST conditions at the transcriptome level. Subsequent pairwise heat mapping and principal component analysis gave further weight to the similarity. At the individual gene level, expressional analysis of representative well-known genes as well as novel genes showed a comparable amount at mRNA and protein levels in ECs under ST and OS conditions. In conclusion, the present work compared the whole transcriptome of HCAECs under different shear stress conditions at the transcriptome level as well as at the individual gene level. We found that cultured ECs are significantly different from those under LS conditions. Thus using cells under ST conditions is unlikely to elucidate endothelial physiology. Given the revealed high similarities of the endothelial transcriptome under OS and ST conditions, it may be helpful to understand the underlying mechanisms of OS-induced endothelial dysfunction from static cultured endothelial studies.

Dataset Information

Transport of ellipsoid fibers in oscillatory shear flows: Implications for aerosol deposition in deep airways.

Publications

Transport of ellipsoid fibers in oscillatory shear flows: Implications for aerosol deposition in deep airways.

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