Inhomogeneities and phase separation in pulmonary surfactant extracts

• Applicant: Tiago Mendes Ferreira, Ph.D.
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271742075

Knowing the molecular structure and dynamics of pulmonary surfactant (PS) is of great interest for the development of exogenous surfactant based medical lung treatments. The state-of-the-art is that PS forms a multi-layer system with a coexistence of distinct bilayer phases. However, the particular phases that occur are still a matter of discussion, as both, a coexistence of fluid lamellar (L_alpha) phases or a coexistence of fluid lamellar with solid-like gel phases are possible explanations for the current experimental data available. We propose to solve this problem by further developing and applying advanced solid-state nuclear magnetic resonance (NMR) methods to characterise the molecular dynamics in lung surfactant systems, with special focus on detecting heterogeneous domains with dynamics in the relevant ms-microsec range, i.e., in the so-called intermediate regime that poses specific challenges to NMR methods. Suitable methods will be tested and established on the example of simple surfactant models of the main components of lung surfactant such as DPPC, cholesterol and the hydrophobic proteins SP-B and SP-C. Such model systems will present a coexistence of distinct gel and liquid phases with intermediate motions and fast motions only, respectively , and we will design and apply NMR methods that are suitable to (i) selectively detect the distinct phases and determine their chemical compositions, (ii) characterise quantitatively the molecular structure and dynamics in both phases, and (iii) determine the domain size distribution of the discontinuous phase. These methods will then be applied to extracts of natural lung surfactant and to surfactants that are currently used in lung treatments. The implementation of the new experiments, specifically homo- and heteronuclear dipolar recoupling, double-quantum and spin diffusion methods, will be aided by dynamic spin dynamics simulations.

• DFG Programme: Research Grants