scholarly journals The single GUV method for revealing the functions of antimicrobial, pore-forming toxin, and cell-penetrating peptides or proteins

2014 ◽  
Vol 16 (30) ◽  
pp. 15752-15767 ◽  
Author(s):  
Md. Zahidul Islam ◽  
Jahangir Md. Alam ◽  
Yukihiro Tamba ◽  
Mohammad Abu Sayem Karal ◽  
Masahito Yamazaki
Keyword(s):  
Rate Constants ◽  
Lipid Membranes ◽  
Pore Formation ◽  
Cell Penetrating Peptides ◽  
Elementary Processes ◽  
Cell Penetrating

The single GUV method provides detailed information on the elementary processes of peptide/protein-induced pore formation in lipid membranes and the entry of peptides into a GUV; specifically, the GUV method provides the rate constants of these processes.

scholarly journals Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Andreas Weinberger ◽  
Vivien Walter ◽  
Sarah R. MacEwan ◽  
Tatiana Schmatko ◽  
Pierre Muller ◽  
...  
Keyword(s):  
Self Assembly ◽  
Lipid Membranes ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

scholarly journals Potassium channels, megapolarization, and water pore formation are key determinants for cationic cell-penetrating peptide translocation into cells

2020 ◽  
Author(s):  
Evgeniya Trofimenko ◽  
Gianvito Grasso ◽  
Mathieu Heulot ◽  
Nadja Chevalier ◽  
Marco A. Deriu ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Pore Formation ◽  
Transmembrane Potential ◽  
Cellular Membrane ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

SummaryCell-penetrating peptides (CPPs) allow intracellular delivery of cargo molecules. CPPs provide efficient methodology to transfer bioactive molecules in cells, in particular in conditions when transcription or translation of cargo-encoding sequences is not desirable or achievable. The mechanisms allowing CPPs to enter cells are ill-defined and controversial. This work identifies potassium channels as key regulators of cationic CPP translocation. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 positively modulate CPP cellular direct translocation by reducing transmembrane potential (Vm). Cationic CPPs further decrease the Vm to megapolarization values (about −150 mV) leading to the formation of ∼2 nm-wide water pores used by CPPs to access the cell’s cytoplasm. Pharmacological manipulation to lower transmembrane potential boosted CPPs cellular uptake in zebrafish and mouse models. Besides identifying the first genes that regulate CPP translocation, this work characterizes key mechanistic steps used by CPPs to cross cellular membrane. This opens the ground for pharmacological strategies augmenting the susceptibility of cells to capture CPP-linked cargos in vitro and in vivo.

Label-free quantification of cell-penetrating peptide translocation into liposomes

2016 ◽  
Vol 8 (23) ◽  
pp. 4608-4616 ◽  
Author(s):  
Marie-Lise Jobin ◽  
Isabel D. Alves
Keyword(s):  
Small Molecules ◽  
Lipid Membranes ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Label Free ◽  
Label Free Quantification ◽  
Cell Penetrating ◽  
Free Quantification ◽  
Peptide Translocation

Cell penetrating peptides (CPPs) are small molecules capable of crossing lipid membranes and transporting cargos of varied sizes and nature inside cells.

scholarly journals Effect of arginine-rich cell penetrating peptides on membrane pore formation and life-times: a molecular simulation study

2014 ◽  
Vol 16 (38) ◽  
pp. 20785-20795 ◽  
Author(s):  
Delin Sun ◽  
Jan Forsman ◽  
Mikael Lund ◽  
Clifford E. Woodward
Keyword(s):  
Molecular Simulation ◽  
Simulation Study ◽  
Pore Formation ◽  
Molecular Simulations ◽  
Cell Penetrating Peptides ◽  
Flip Flop ◽  
Membrane Pore ◽  
Membrane Pores ◽  
Cell Penetrating

Molecular simulations show that arginine-rich peptides can stabilize transient membrane pores induced by lipid flip-flop.

Thermodynamics of cell penetrating peptides on lipid membranes: sequence and membrane acidity regulate surface binding

2020 ◽  
Vol 22 (40) ◽  
pp. 23399-23410
Author(s):  
Pedro G. Ramírez ◽  
Mario G. Del Pópolo ◽  
Jorge A. Vila ◽  
Gabriel S. Longo
Keyword(s):  
Lipid Membranes ◽  
Cell Penetrating Peptides ◽  
Surface Binding ◽  
Cell Penetrating ◽  
Acidic Lipids

Acidic lipids respond to pH in ways that fully promote or deplete the surface accumulation of cell penetrating peptides.

scholarly journals How arginine derivatives alter the stability of lipid membranes: dissecting the roles of side chains, backbone and termini

2021 ◽  
Vol 50 (2) ◽  
pp. 127-142 ◽  
Author(s):  
Sarah F. Verbeek ◽  
Neha Awasthi ◽  
Nikolas K. Teiwes ◽  
Ingo Mey ◽  
Jochen S. Hub ◽  
...  
Keyword(s):  
Free Energy ◽  
Lipid Bilayers ◽  
Lipid Membranes ◽  
Pore Formation ◽  
Line Tension ◽  
Md Simulations ◽  
Substantial Effect ◽  
Cell Penetrating Peptides ◽  
Free Energy Calculations ◽  
The Stability

AbstractArginine (R)-rich peptides constitute the most relevant class of cell-penetrating peptides and other membrane-active peptides that can translocate across the cell membrane or generate defects in lipid bilayers such as water-filled pores. The mode of action of R-rich peptides remains a topic of controversy, mainly because a quantitative and energetic understanding of arginine effects on membrane stability is lacking. Here, we explore the ability of several oligo-arginines R$$_n$$ n and of an arginine side chain mimic R$$_\mathrm {Side}$$ Side to induce pore formation in lipid bilayers employing MD simulations, free-energy calculations, breakthrough force spectroscopy and leakage assays. Our experiments reveal that R$$_\mathrm {Side}$$ Side but not R$$_n$$ n reduces the line tension of a membrane with anionic lipids. While R$$_n$$ n peptides form a layer on top of a partly negatively charged lipid bilayer, R$$_\mathrm {Side}$$ Side leads to its disintegration. Complementary, our simulations show R$$_\mathrm {Side}$$ Side causes membrane thinning and area per lipid increase beside lowering the pore nucleation free energy. Model polyarginine R$$_8$$ 8 similarly promoted pore formation in simulations, but without overall bilayer destabilization. We conclude that while the guanidine moiety is intrinsically membrane-disruptive, poly-arginines favor pore formation in negatively charged membranes via a different mechanism. Pore formation by R-rich peptides seems to be counteracted by lipids with PC headgroups. We found that long R$$_n$$ n and R$$_\mathrm {Side}$$ Side but not short R$$_n$$ n reduce the free energy of nucleating a pore. In short R$$_n$$ n , the substantial effect of the charged termini prevent their membrane activity, rationalizing why only longer $$\mathrm {R}_{n}$$ R n are membrane-active.

Sign in / Sign up

Export Citation Format

Share Document