Particle deposition, clearance and interaction with lung surfactant

Numerical moelling of three areas of human lung: (a) Particle deposition, (b) Mucociliary Clearance and (c) particle lung interaction

Computational Fluid Dynamics study of particle deposition in the CT-Scan based lung surface

Particulates inhaled by human during normal breathing sometimes affect the lung cells. This project will develop a novel modelling framework capable of accurately representing the deposition zones and the slow clearance zone of the real bifurcation. The framework integrates models for CT Scans/MRI images, particles flow and mucus layer movement and accounts for particle deposition and clearance by multi-scale approach. It will provide a powerful tool to gain new insight and deepened understanding of the mechanisms of particle deposition and subsequent clearance through mucus movement. Therefore, it will significantly improve the drug delivery for asthma and cancer patients as well as other related diseases.

Muco-ciliary Transport in patients with chronic respiratory diseases using an advanced numerical method

Aerosols are solid or liquid particles suspension in air, which are naturally present in the form of dust, smoke, etc. From the toxicologic point of view, these particles have the potential of being biologically active in susceptible individuals. Therefore, it is vital to understand how these deposited particles are being cleared out of the respiratory system. Mucociliary clearance, the transport of foreign particles deposited on the lung airway surfaces by a blanket of mucus, is recognized as the principle as well as the fastest clearance mechanism in the trachea-bronchial region where the an array of cilia beat rapidly and propel the mucus, together with entrapped particulate materials (that might damage the lungs), from the airways towards the larynx. This research project aims to develop an advanced numerical model which can simulate the mucociliary clearance in a more realistic manner by considering a flexible structure for cilia beating on the lung epithelial cells and transporting airway surface liquid in normal functioning and disease.

Modelling of Gold nanoparticle with or without drug coated interaction into lung surfactant at the molecular scale

With the dawn of nanosciences, the use of nanomaterials has become widespread in various scientific fields from cosmetics and electronics to medicines and their increasing use has led to the release of nanoparticles (NPs) in the environment. While NPs featuring gold cores (AuNPs) have been in use for decades for targeted drug delivery of cancer drugs, one important problem is that exposure to AuNPs from the environment is a potential health hazard. The lungs are easily exposed to these particles present in the atmosphere, making contact with the inner surface of the alveolus called the lung surfactant (LS). LS monolayer which consists of lipids, four types of proteins and other molecules, is the first barrier that these NPs encounters in order to enter the circulatory system. Despite exhaustive experimental studies, the molecular-level mechanism behind the translocation and permeation of environmental and engineered AuNPs into the LS is still poorly understood. Coarse-grained (CG) molecular dynamics (MD) will be carried out to study a model pulmonary surfactant (PS) film interacting with AuNPs of different sizes, shapes and concentration. Additionally, similar simulations will be carried out in presence of cholesterol and proteins SP-B and SP-C to investigate their effect on interactions with AuNPs at the air-water interface. A series of molecular-scale structural and dynamical properties of the surfactant film in the absence and presence of nanoparticle will be analysed, including phase behaviour, order parameter, pressure area isotherm, surface charge density, and area per lipid. Our preliminary results of CG system consisting DPPC: POPG lipids (7:3) and 3nm AuNPs show that AuNPs quickly interact with the lipid monolayer and create rupture in the monolayer. The nano-bio interactions impede the surface activity of the surfactant system during the normal breathing process and is in agreement with previously published experimental data by Bakshi et al. Our results will bring to the forefront the concern of the inhalation toxicity of AuNPs and their role in pulmonary disease. This PhD project will also provide guidelines for the future design of inhaled NPs with minimized side effects.

Related publications

Journal Publications

M.S. Islam, Y.T. Gu, A. Farkas, G. Paul, S. C. Saha, “Helium-Oxygen Mixture Model for Particle Transport in CT-Based Human Lung”, International Journal of Environmental Research and Public Health, 17 (2020) pp. 3574. [IF: 2.468] Q2.
P. Singh , V. Raghav, V. Padhmashali, G. Paul, M.S. Islam, S. C. Saha, “Airow and particle transport prediction through stenosis airway”, International Journal of Environmental Research and Public Health, 17 (2020) pp. 1119. [IF: 2.468] Q2.
M.S. Islam, G. Paul, H.X. Ong, P.M. Young, Y.T. Gu, S. C. Saha, “A Review of respiratory anatomical development, air ow characterization and particle deposition”, International Journal of Environmental Research and Public Health, 17 (2020) pp. 380. [IF: 2.468] Q2
S. M. Vanaki, D. Holmes, S. C. Saha, J. Chen, R. J. Brown, P. G. Jayathilake, “Muco-ciliary clearance: A review of modelling techniques”, Journal of Biomechanics, 99 (2020) pp. 109578 [IF: 2.576]. Q1.
M. S. Islam, S. C. Saha, E. Sauret, H. Ong, P. Young, Y. T. Gu, “Euler-Lagrange approach to investigate respiratory anatomical shape eects on aerosol particle transport and deposition” Toxicology Research and Application, 3 (2019) pp. 1 – 15.
Q. Gu, S. Qi, Y. Yue, J. Shen, B. Zhang, W. Sun, W. Qian, M. S. Islam, S. C. Saha, J. Wu, “Structural and functional alternations of the tracheobronchial tree after left upper pulmonary lobectomy for lung cancer”, BioMedical Engineering OnLine, 18 (2019) Article number: 108 [I.F. 1.676]. Q2.
M. S. Islam, S. C. Saha, T. Gemci, E. Sauret, I. A. Yang, Z. Ristovski, Y. T. Gu, “Euler-Lagrange prediction of diesel-exhaust polydisperse particle transport and deposition: Anatomy and turbulence eects” Nature Scientic Reports, 9 (2019) Article number: 12423 (16 pages). [IF: 4.525]. Q1.
S. I. Hossain, N. S. Gandhi, Z. E. Hughes, Y. T. Gu, S. C. Saha, “Molecular insights on the interference of simplied lung surfactant models by gold nanoparticle pollutants”, BBA Biomembranes, 1861 (2019) pp. 1458 – 1467. [IF: 3.790]. Q1
M. S. Islam, S. C. Saha, E. Sauret, T. Gemci, I. A. Yang, Y. T. Gu, “Polydisperse microparticle transport and deposition to the terminal bronchioles in a heterogeneous vasculature tree” Nature Scientic Reports, 8 (2018) Article number: 16387 (9 pages). [IF: 4.525. Q1.
M. S. Islam, S. C. Saha, E. Sauret, T. Gemci, I. A. Yang, Y. T. Gu, “Ultrane particle transport and deposition in a large scale 17-generation lung model” Journal of Biomechanics, 64 (2017) pp. 9 { 18, [IF: 2.576]. Q1.
M. S. Islam, S.C. Saha, E. Sauret, I. Yang, Y. Gu, “Pulmonary aerosol transport and deposition analysis in upper 17 generations of the human respiratory tract.” Journal of Aerosol Science, 108, (2017), pp. 29 – 43 [IF: 2.240] Q2.

Conference Proceedings

M. Z. Islam, S. I. Hossain, E. Deplazes, S. Bhowmick S. C. Saha, “Molecular Dynamics Study of Prednisolone Concentration on Cholesterol Based Lung Surfactant Monolayer” Proceeding of the 13th International Conference on Mechanical Engineering (ICME2019), 18 – 20 December 2019, BUET, Dhaka, Bangladesh.
M. S. Islam, Y. T. Gu, S. C. Saha, “Helium-Oxygen Mixture Model for Particle Transport in CT-Based MouthThroat and Upper airways ” Proceeding of the Australasian Conference on Computational Mechanics, Tasmania, Australia, 27 – 29 November 2019.
M. S. Islam, Y. T. Gu, S. C. Saha, “Helium-Oxygen Mixture Model for Particle Transport in CT-Based MouthThroat and Upper airways ” Proceeding of the Australasian Conference on Computational Mechanics, Tasmania, Australia, 27 – 29 November 2019.
S. C. Saha, M. S. Islam, Z. Luo, “Ultrane Particle Transport and Deposition in the Upper Airways of a CT-Based Realistic Lung” Proceeding of the 21st Australasian Fluid Mechanics Conference, Adelaide, Australia, 10 – 13 December 2018.
S. C. Saha, M. S. Islam, M. M. Molla, “Aerosol Particle Transport and Deposition in a CT-Scan Based Mouth-Throat Model”, Proceedings of the 8th BSME International Conference on Thermal Engineering, 19 – 21 December, 2018, Dhaka, Bangladesh.
M. S. Islam, S. C. Saha, P. M. Young, “Aerosol Particle Transport and Deposition in a CT- Based Lung Airway for Helium-Oxygen Mixture” Proceeding of the 21st Australasian Fluid Mechanics Conference, Adelaide, Australia, 10 – 13 December 2018. 2017
M.S. Islam, S. C. Saha, E. Sauret, Y.T. Gu, “Transport and Deposition in the Terminal Bronchioles of Large Scale 17-Generation Model” Proceedings of the 8th International Conference on Computational Methods (ICCM2017), 25 { 29 July 2017, Guilin, Guangxi, China.
S.I. Hossain, S. C. Saha, N.S. Gandhi, E. Sauret, Y.T. Gu, “Molecular dynamics simulation study of a pulmonary surfactant monolayer with Gold nanoparticles”, MM2017 Conference, 27 – 29 September 2017, Curtin University, Western Australia.
M.S. Islam, S. C. Saha, E. Sauret, Y.T. Gu, “Diesel Exhaust Particle Transport and Deposition in Upper 4 Generations of the CT-Scan based Lung Airways”, Proceedings of the 20th Australasian Fluid Mechanics Conference (AFMC2016), 05 { 08 December, 2016, Perth, Australia.
M.S. Islam, S. C. Saha, E. Sauret, Y.T. Gu, “Eects of Velocity on Diesel Exhaust Particle Transport and Deposition in the Central Airways of the Human Lung”, Proceedings of the 2nd Australasian Conference on Computational Mechanics (ACCM2015), 30 November – 01 December 2015, Brisbane, Australia.
M. S. Islam, S. C. Saha, E. Sauret, Y. T. Gu, “Numerical investigation of aerosol particle transport and deposition in realistic lung airway”, Proceedings of the 6th International Conference on Computational Methods (ICCM2015), 14 { 17 July, 2015, Auckland, New Zealand.