Molecular dynamics study of SP-B fragment interactions with model lung surfactant bilayers

Respiration depends on a lung surfactant layer to facilitate changes in surface area at the air-water interface. The 79-amino acid lung surfactant protein SP-B, normally present in dimer form, is essential to the functioning of lung surfactant. One important aspect of lung surfactant function is the recruitment and cycling of surfactant material to and from bilayer reservoirs. Full utilization of surfactant material available in multilamellar reservoirs presumably requires the formation of contacts between adjacent bilayer surfaces and the formation of connections between leaflets of a given surfactant bilayer. Some fragments of SP-B, including the N-terminal segment SP-B_1-25, mimic the effects of full SP-B on model surfactant monolayers and in preparations applied in surfactant-deficient animal model studies. In this work, all-atom molecular dynamics simulations have been carried out on DPPC/POPG model bilayers containing multiple copies of SP-B_1-25 initially oriented along the bilayer surface, across the bilayer, or randomly as well as on model bilayers containing SP-B_1-9 randomly oriented on the bilayer surfaces. These results show that, over the microsecond durations of the simulations, SP-B_1-25 remains largely helical and can be accommodated along the bilayer surface, where it would be available to interact with adjacent bilayers, or across the bilayer which results in local perturbation of the bilayer surface. These observations provide some insight into the possible capacity of the N-terminal segment of SP-B to mediate both interbilayer and intrabilayer interactions that are presumably involved in the lipid assembly reorganization necessary to facilitate surfactant recruitment and recycling from bilayer reservoirs.