Development of a Biomimetic Lung Surfactant Replacement

Northwestern University, Evanston IL

Investigators

Abstract

0101195 Barron In continuation of work that is presently funded by a one-year NSF SGER grant, the PI's propose to elaborate on this novel class of structured, sequence-specific heteropolymers to develop close mimics of natural SP-B and SP-C, that will be stable and biocompatible for in vivo use. This medically-relevant research project offers potential for broad impact on the field of biomaterials engineering, by demonstrating the usefulness of non-natural, sequence-specific polymers for biomimicry. The aims are: (1) To design, synthesize, chromatographically purify, and spectroscopically characteize the secondary strutures of peptoid mimics of helical, amphipathic LS proteins SP-B and SP-C; (2) To perform in vitro biophysical characterization of peptoid SP mimics as spreading agents for biomimetic lipid admixtures, carrying out studies on a pulsating bubble surfactometer and a Langmuir-Wilhelmy surface balance, and making comparisons to LS containing natural petpides; (3) To formulate a therapeutic, biomimetic LS replacement containing both phospholipids and SP mimics, that is effective, bioavailable, biocompatible, and more cost-effective than animal LS; (4) To carry out in vivo testing of optimized biomimetic LS replacements in a murine model of RDS, in collaboration with Brigham and Women's Hospital; and, (5) To deepen the present fundamental understanding of the relationship between LS protein structural features and biophysical functioning in phospholipid surface films.