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Title: Membrane-selective nanoscale pores in liposomes by a synthetically evolved peptide: implications for triggered release
Peptides that form nanoscale pores in lipid bilayers have potential applications in triggered release, but only if their selectivity for target synthetic membranes over bystander biomembranes can be optimized. Previously, we identified a novel family of α-helical pore-forming peptides called “macrolittins”, which release macromolecular cargoes from phosphatidylcholine (PC) liposomes at concentrations as low as 1 peptide per 1000 lipids. In this work, we show that macrolittins have no measurable cytolytic activity against multiple human cell types even at high peptide concentration. This unprecedented selectivity for PC liposomes over cell plasma membranes is explained, in part, by the sensitivity of macrolittin activity to physical chemical properties of the bilayer hydrocarbon core. In the presence of cells, macrolittins release all vesicle-entrapped cargoes (proteins and small molecule drugs) which are then readily uptaken by cells. Triggered release occurs without any direct effect of the peptide on the cells, and without vesicle–vesicle or vesicle–cell interactions.  more » « less
Award ID(s):
1709892
NSF-PAR ID:
10299047
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Nanoscale
Volume:
13
Issue:
28
ISSN:
2040-3364
Page Range / eLocation ID:
12185 to 12197
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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