Biochemistry and Models for Function

tte biophysical utility of IRRAS measurements will be demonstrated in the current chapter through studies of the structure, orientation, and conformational flexibility of peptides important for understanding the pulmonary surfactant system. Some background is provided in the following for reference.

Fig. 3.6. A Coordinate systems for the IRRAS simulations. Top left: A local right-handed Cartesian coordinate system abc is attached to the p-strand such that the c-axis is in the direction of the strand, the a-axis is in the plane of the sheet perpendicular to the c-axis, and the b-axis is perpendicular to both the a-axis and the c-axis. The orientation of the transition moment vector, associated with the amide I band in the local system is described by a polar angle a and

Angle of Incidence

Fig. 3.6. A Coordinate systems for the IRRAS simulations. Top left: A local right-handed Cartesian coordinate system abc is attached to the p-strand such that the c-axis is in the direction of the strand, the a-axis is in the plane of the sheet perpendicular to the c-axis, and the b-axis is perpendicular to both the a-axis and the c-axis. The orientation of the transition moment vector, associated with the amide I band in the local system is described by a polar angle a and

Pulmonary surfactant is a mixture of lipids and proteins that forms a monolayer film at the air/alveolar interface in the terminal airway of the mammalian lung, tte major function of surfactant is to lower surface tension, thereby reducing the work required to increase lung volume and preventing alveolar collapse, tte pathological consequences of a deficiency in surfactant are severe. Respiratory distress syndrome (RDS) in premature infants and adult RDS (ARDS) are two common conditions.

tte biochemical composition of pulmonary surfactant consists mainly of lipids (90% by weight) and proteins (10% by weight), tte lipid fraction is predominantly DPPC and phosphatidylglycerols (PGs) along with a significant proportion of unsaturated phosphatidylcholines (PCs) and PGs, other phospholipid classes, and cholesterol. ttere are four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D, named in order of their discovery, of which two, SP-B and SP-C, are very hydrophobic and are implicated in controlling the surface properties of surfactant. In particular these proteins have been shown to facilitate in vitro adsorption and spreading of lipids across air/water interfaces (Johansson and Curstedt 1997). In vivo, the physiological importance of SP-B is demonstrated by the observation that neonatal SP-B-deficient mice die at birth from respiratory failure (Lin et al. 1999).

Biophysical studies have tended to focus on two issues, namely (1) the molecular mechanism by which surfactant lipids and proteins interact to facilitate spreading across the interface and (2) the rational design of therapeutic agents, tte former is a nontrivial matter as surfactant in vivo must possess two apparently contradictory attributes. It must be able to form stable films at the high surface pressures (around 70 mN m_1) that form upon exhalation; and it must also be able to spread sufficiently rapidly across the air/alveolar interface to keep up with breathing rates. DPPC is the only major surfactant constituent that can form stable monolayers at 70 mN m_1 under compressive forces; however, it spreads too slowly during surface area expansion to be effective in vivo. To address this issue, Goerke and Clements (1986) proposed that for films to be stable, a process must occur during which the surface concentration of DPPC was enhanced at high pressures, tte process, not defined in molecular structure terms, was labeled "squeeze-out."

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