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The effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructure

Carsten Schleh12, Christian Mühlfeld3, Karin Pulskamp4, Andreas Schmiedl5, Matthias Nassimi16, Hans D Lauenstein12, Armin Braun1, Norbert Krug1, Veit J Erpenbeck12 and Jens M Hohlfeld12*

Author Affiliations

1 Fraunhofer Institute of Toxicology and Experimental Medicine, Division of Immunology, Allergology and Airway Research, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany

2 Department of Respiratory Medicine, Hannover Medical School, Germany

3 Institute of Anatomy, Division of Histology, University of Bern, Switzerland

4 Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Department of Molecular and Environmental Toxicology, Germany

5 Institute of Functional and Applied Anatomy, Hannover Medical School, Germany

6 Department of Pharmaceutics, Technical University Carolo-Wilhelmina at Braunschweig, Germany

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Respiratory Research 2009, 10:90  doi:10.1186/1465-9921-10-90

Published: 30 September 2009



Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO2) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO2 effects on surfactant ultrastructure were visualized.


A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 μg/ml) of TiO2 NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope.


TiO2 NSP, but not MSP, induced a surfactant dysfunction. For TiO2 NSP, adsorption surface tension (γads) increased in a dose-dependent manner from 28.2 ± 2.3 mN/m to 33.2 ± 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (γmin) slightly increased from 4.8 ± 0.5 mN/m up to 8.4 ± 1.3 mN/m (p < 0.01) at high TiO2 NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both γads (63.6 ± 0.4 mN/m) and γmin (21.1 ± 0.4 mN/m). Interestingly, TiO2 NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae.


TiO2 nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.