Project Description

Cell death resulting from pore formation in cell membranes by peptides has important consequences in biology. An important function of pore forming peptides is in the defense of plants and animals against invading microbes. These antimicrobial peptides could be very useful for combating drug resistant microbes. It is also one of the causes of neurological disorders such as Alzheimers disease. In these cases, fibrils formed by aggregation of amyloid beta peptides form pores in neuronal cell membranes causing death. Elucidation of this mechanism as a result of the work proposed here will help greatly in the development of guidelines for design of antimicrobial peptides to replace antibiotics and strategies for effective treatment of neurological disorders. A general framework will be developed for the prediction of pore formation by peptide of any amino acid composition and sequence for bacterial as well as mammalian cell membranes. This framework is based on molecular dynamics simulation of interaction of peptides with lipid bilayer and nucleation and growth of pores in lipid bilayers accounting for detailed pore structure as well as intermolecular interactions. Experimental verification of the methodology will be carried out using fluorescent dye leakage in liposomes as well as by microbial deactivation studies.  

Start Date

June 1, 2019

Postdoc Qualifications

Co-advisors

Ganesan Narsimhan
Department of Agricultural and Biological Engineering
email: narsimha@purdue.edu 

Arun Bhunia
Department of Food Science
email: bhunia@purdue.edu

References

1. Xiang, N., Lyu, Y., Zhu, X., & Narsimhan, G. (2018). Investigation of the interaction of amyloid β peptide (11–42) oligomers with a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane using molecular dynamics simulation. Physical Chemistry Chemical Physics, 20(10), 6817-6829.