Understanding how charged biopolymers destabilize membranes

Cell membranes form the barrier by which cells interact with the external environment. As such, understanding the nature of how biopolymers interact with the membrane and the mechanisms by which different types of interactions between the biopolymer and membrane lead to changes in membrane structure will lead to fundamental understanding of cell function.

This project will specifically examine the weak forces involved in the interaction between charged biopolymers, like antimicrobial peptides, and cell membranes, and explore membrane perturbation, adhesion, and signaling interactions. Membrane structure changes will be quantified using techniques include x-ray diffuse scattering (XDS) and circular dichroism (CD).

The project will create hands-on experiences for undergraduate researchers (10-15/year) who desire to carry out research in the PI’s biophysics lab. The project will fund one postdoctoral associate who has been trained in similar biophysical methods during her Ph.D. Besides mentoring students and a postdoc in the lab, the PI will conduct outreach activities, which primarily involve judging at several science fairs each year, including the Pennsylvania Junior Academy of Sciences science fair, the Sigma Xi poster competition at the Meeting of the Minds at Carnegie Mellon, and the Regeneron International Science and Engineering Fair.

The forces involved in the interaction between charged biopolymers and cell membranes are electrostatic, van der Waals and fluctuation. To investigate these forces, synthetic charged biopolymers are employed to interact with lipid model membranes that are mimics of real membranes (eukaryotic, bacterial, and viral cell membranes). Recent work from the PI lab has demonstrated a close correlation between measured membrane material properties and membrane destabilization of bacterial and eukaryotic cell membranes interacting with three biopolymers: colistin (a natural-occurring protein biopolymer) and two novel engineered biopolymers, WLBU2 and D8.

These three cationic biopolymers are antimicrobial peptides, a new form of antibiotic. The project will use x-ray diffuse scattering to obtain material parameters of lipid model membranes that are mimics of bacterial and eukaryotic cell membranes as novel engineered biopolymers are added. The PI with collaborators will design the protein biopolymers and test them for membrane destabilization of clinical bacterial isolates both in vitro and in vivo as part of their research program.

The PI’s biophysics lab will determine changes in elasticity and structure of biomimetic membranes using XDS, and changes in biopolymer secondary structure using CD, as the biopolymers encounter the lipid model membranes. Location of biopolymer in the membrane will be determined using neutron scattering techniques and the atomistic details will be obtained using molecular dynamics simulations.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.