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Tensiometric and Phase Domain Behavior of Lung Surfactant on Mucus-Like Viscoelastic Hydrogels Daniel M Schenck, and Jennifer Fiegel ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b00294 • Publication Date (Web): 19 Feb 2016 Downloaded from http://pubs.acs.org on February 22, 2016
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ACS Applied Materials & Interfaces
Tensiometric and Phase Domain Behavior of Lung Surfactant on Mucus-Like Viscoelastic Hydrogels Daniel M. Schenck1, Jennifer Fiegel1,2,*
1
Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa
City, IA, 52242, USA.
2
Department of Chemical and Biochemical Engineering, The University of Iowa, Iowa City, IA, 52242,
USA.
* To whom correspondence should be addressed: Jennifer Fiegel, The University of Iowa, 4133 Seamans Center for the Engineering Arts and Sciences, Iowa City, IA, 52242, USA. Email:
[email protected].
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ABSTRACT Lung surfactant has been observed at all surfaces of the airway lining fluids and is an important contributor to normal lung function. In the conducting airways, the surfactant film lies atop a viscoelastic mucus gel. In this work, we report on the characterization of the tensiometric and phase domain behavior of lung surfactant at the air-liquid interface of mucus-like viscoelastic gels. Poly(acrylic acid) hydrogels were formulated to serve as a model mucus with bulk rheological properties that matched those of tracheobronchial mucus secretions. Infasurf® (Calfactant), a commercially available pulmonary surfactant derived from calf lung extract, was spread onto the hydrogel surface. The surface tension lowering ability and relaxation of Infasurf films on the hydrogels was quantified and compared to Infasurf behavior on an aqueous subphase. Infasurf phase domains during surface compression were characterized by fluorescence microscopy and phase shifting interferometry. We observed that increasing the bulk viscoelastic properties of the model mucus hydrogels reduced the ability of Infasurf films to lower surface tension and inhibited film relaxation. A shift in the formation of Infasurf condensed phase domains from smaller, more spherical domains to large, agglomerated, multilayer structures was observed with increasing viscoelastic properties of the subphase. These studies demonstrate that the surface behavior of lung surfactant on viscoelastic surfaces, such as those found in the conducting airways, differs significantly from aqueous, surfactant-laden systems.
KEYWORDS bulk rheology, conducting airways, fluorescence microscopy, hydrogel, lung surfactant, mucus, surface tension, domain morphology
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ACS Applied Materials & Interfaces
INTRODUCTION Lining the entirety of the lung epithelium, the airway lining fluids serve to hydrate and protect the underlying tissue. These fluids function as dynamic semipermeable barriers that allow the exchange of gases, nutrients and water, but limit the transport of foreign material to the epithelium1. The structure of the fluids plays an important role in their functionality. In the conducting airways, the airway lining fluid develops as a thick (~10-30 µm in the tracheobronchial region) multi-phase fluid. The periciliary fluid layer coats the epithelial surface and is occupied by cilia that extend from the cell surface to the mucus gel and facilitate mucociliary clearance. The mucus gel layer lying atop the periciliary layer is composed of a complex network of macromolecules, including cross-linked glycoproteins2 and proteins, as well as ions and water. Due to its network structure, the mucus layer exhibits viscoelastic behavior in response to external deformation. Rheological measurements of tracheobronchial mucus demonstrate its elastic behavior at physiological shear rates (breathing) and a shear thinning viscosity profile3-4. The viscoelastic properties of mucus are important for maintaining function in the conducting airways, as the mucus gel acts to entrap foreign particles for the protection of the underlying epithelium and facilitates the continuing function of the mucociliary escalator through energy storage5. At the air-fluid interface of the airways, lung surfactant adsorbs to the fluid interface and appears as a distinguishable, mostly continuous surface layer observed in various animals6-7. Lung surfactant reduces the surface tension of the airway fluids from ~30-34 mN/m in the trachea8 to
