Received: 1 July, 2009. Accepted: 27 October, 2009.
Invited Review
Dynamic Biochemistry, Process Biotechnology and Molecular Biology ©2009 Global Science Books
Pulmonary Surfactant Nanostructures and their Implications
Anubhav Kaviratna Apurva Shah Shailendra Singh Rao Rinti Banerjee
*
Department of Biosciences and Bioengineering, Centre for Research in Nanotechnology and Science, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
Corresponding author: * rinti@iitb.ac.in
ABSTRACT
A surface active material that lines our lungs is referred to as pulmonary surfactant (PS) and consists of a self-assembled complex of
nanostructures (NSs) rich in phospholipids (PLs) and proteins that lie at the air-liquid interface of the pulmonary alveoli. It serves a very
critical function during respiration by dynamically modifying surface tension. It is responsible for the attainment of near zero surface
tension at the end of expiration. PLs are assisted by surfactant proteins to form lamellar bodies of 500 nm to 1-2 µm in size, nanotubes of
2-5 nm height, monolayer films of domain heights of 0.8 to 5 nm and multilayered stacked reservoir phases during the surfactant life
cycle. During respiration, the PL molecules present in the surfactant film undergo molecular rearrangement to alter surface tension and
maintain high lung compliance. Destruction or absence of PS and/or the above mentioned NSs can occur due to genetic variations, direct
or indirect lung injuries and lead to many respiratory diseases. Surfactant NSs, their composition and the packing of the surfactant
monolayer are altered in diseased states. Transmission electron microscopy and atomic force microscopy are useful techniques to evaluate
pulmonary nanostructures and confirm their alterations in diseased states. Drug-loaded nanoparticles (NPs), when delivered in the respira-
tory system, first interact with pulmonary surfactant. These interactions can alter drug release, residence time and cellular interactions of
the nanoparticles. Similarly, pulmonary surfactant also influences the cellular response and toxicity of respirable environmental fine
particles. This review describes the various nanostructures formed by PS, the interactions NPs with PS and their implications.
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Keywords: drug delivery, lamellar bodies, monolayer, nanostructures, pulmonary surfactant, tubular myelin
Abbreviations: ABCA3, ATP-binding cassette transporter A3; AE2, alveolar type II; AFM, atomic force microscopy; CF, cord factor;
DMPC, dimyristoyl phosphatidylcholine; DPPG, dipalmitoyl phosphatidylglycerol; DPPC, dipalmitoyl phosphatidylcholine; LA, large
aggregate; LB, lamellar body; LC, liquid condensed; LE, liquid expanded; LE-LC, liquid expanded-liquid condensed; LPS, lipopoly-
saccharide; MA, mycolic acid; NP, nanoparticle; NS, nanostructure; PAMAM, poly-amidoamine; PC, phosphatidyl choline; PE,
phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PLGA, polylactic-co-glycolic acid; PL, phospholipid;
POPC, palmitoyloleoyl phosphatidylcholine; POPG, palmitoyloleoyl phosphatidylglycerol; PS, pulmonary surfactant; SA, small
aggregate; SP, surfactant protein; TEM, transmission electron microscopy; TM, tubular myelin
CONTENTS
INTRODUCTION ................................................................................................................................................................................ 1
PULMONARY SURFACTANT: COMPOSITION................................................................................................................................. 2
Lipids .............................................................................................................................................................................................. 2
Surfactant proteins............................................................................................................................................................................ 2
PS NANOSTRUCTURES: FORMATION, FUNCTION AND IMPLICATIONS .................................................................................... 4
Lamellar bodies (LBs) ...................................................................................................................................................................... 4
Nanotubes of tubular myelin ............................................................................................................................................................. 5
PS film............................................................................................................................................................................................. 5
Incorporation of the surfactant with the surface and bilayer-monolayer contacts ................................................................................. 5
Enrichment of the DPPC in monolayer .............................................................................................................................................. 6
Surface film reservoir ....................................................................................................................................................................... 6
Reorganisation of the surfactant film upon expansion ........................................................................................................................ 6
Recycling of surfactant material ........................................................................................................................................................ 6
PHASE TRANSITIONS IN DPPC MONOLAYER AND PS FILMS ..................................................................................................... 6
Lipid raft model ............................................................................................................................................................................... 7
Supercooled surfactant, a two dimensional alloy................................................................................................................................ 7
ALTERATIONS IN NSs AND PHASES OF PS IN DISEASED STATES ............................................................................................... 7
PS INTERACTIONS WITH NPs .......................................................................................................................................................... 8
Interactions with environmental fine particulates ............................................................................................................................... 8
Interactions with drug-loaded particles .............................................................................................................................................. 9
FUTURE PERSPECTIVES .................................................................................................................................................................. 9
REFERENCES ..................................................................................................................................................................................... 9
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INTRODUCTION
The alveolar epithelium in the lungs is covered with a liquid
lining (Goerke 1974). This alveolar lining basically consists
of an aqueous subphase covered by a film of pulmonary
surfactant (PS). PS is a complex mixture of lipids (~90%)
and proteins (~10%) secreted by the alveolar epithelial type
II (AE2) cells into the alveolar space (Rooney et al. 1994;
Frick et al 2001; Andreeva et al. 2007). PS forms many
lipid–protein nanostructures (NSs) like the lamellar bodies
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