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REVIEW
Contents Vol 73(3)

The Mechanism of Membrane Permeabilization by Peptides: Still an Enigma*

William C. Wimley https://orcid.org/0000-0003-2967-5186 A C and Kalina Hristova https://orcid.org/0000-0003-4274-4406 B C
+ Author Affiliations
- Author Affiliations

A Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA.

B Department of Materials Science and Engineering, Institute for NanoBioTechnology, and Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.

C Corresponding authors. Email: wwimley@tulane.edu; kh@jhu.edu




William C. Wimley is originally from Monroe, Connecticut. He studied biophysics at the University of Connecticut (B.S., 1985) and biochemistry at the University of Virginia (Ph.D., 1990) where his dissertation work focused on the interactions between lipids in synthetic membranes. As a postdoc at the University of California, Irvine, he began a lifelong study of peptides in membranes. The current focus of the Wimley laboratory is synthetic molecular evolution of membrane permeabilizing, pore-forming, cell penetrating, membrane translocating, antibacterial, and antiviral peptides.


Kalina Hristova received her B.S. and M.S. degrees in physics from the University of Sofia, Bulgaria, and her Ph.D. degree in mechanical engineering and materials science from Duke University, USA. She did post-doctoral work at the University of California, Irvine. She is now a Professor of Materials Science and Engineering at the Institute for NanoBioTechnology at Johns Hopkins University. Dr Hristova is the recipient of the 2007 Margaret Oakley Dayhoff award from the Biophysical Society. She was elected Fellow of the American Physical Society in 2016, and Fellow of the American Institute for Medical and Biological Engineering in 2018. The main focus of the research in her laboratory is the physical principles that underlie membrane protein folding and signal transduction across biological membranes.

Australian Journal of Chemistry 73(3) 96-103 https://doi.org/10.1071/CH19449
Submitted: 12 September 2019  Accepted: 4 October 2019   Published: 11 November 2019

Abstract

Peptide-induced permeabilization of lipid vesicles has been measured for decades and has provided many insights into the sequence–structure–function relationships of membrane-active peptides. However, researchers in the field have noted that many experiments show transient permeabilization, in which a burst of leakage occurs immediately after peptide addition, followed by a slow-down or cessation of leakage before all contents have been released. This widely observed, but rarely studied, phenomenon is not explained by standard equilibrium pore models that are commonly invoked in both experimental and computational studies. Here, we discuss observations of transient permeabilization, and we outline a pathway towards understanding this enigmatic phenomenon.


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