Evidence map›Paper›PMID 31422821›Full record

ArticleBiophysical journal2019

Ions Modulate Key Interactions between pHLIP and Lipid Membranes.

Justin Westerfield, Chitrak Gupta, Haden L Scott, Yujie Ye, Alayna Cameron, Blake Mertz, Francisco N Barrera

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. pHLIP Peptides Target Acidity in Activated Macrophages.Molecular imaging and biology · 2022
    Article
  7. Increasing the Realism ofJournal of chemical theory and computation · 2022
    Article
  8. Article
  9. Predicting Membrane-Active Peptide Dynamics in Fluidic Lipid Membranes.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Justin WesterfieldDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee-Knoxville, Knoxville, Tennessee.
Chitrak GuptaC. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia.
Haden L ScottDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee-Knoxville, Knoxville, Tennessee.
Yujie YeDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee-Knoxville, Knoxville, Tennessee.
Alayna CameronDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee-Knoxville, Knoxville, Tennessee.
Blake MertzC. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia; WVU Cancer Institute, West Virginia University, Morgantown, West Virginia. Electronic address: blake.mertz@mail.wvu.edu.
Francisco N BarreraDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee-Knoxville, Knoxville, Tennessee. Electronic address: fbarrera@utk.edu.
University of Tennessee at Knoxville · USWest Virginia University · USKnoxville College · US

Funding

Transmembrane Peptides for Targeting Acidosis - Equipment SupplementR01GM120642 · NIGMS · UNIVERSITY OF TENNESSEE KNOXVILLE · PI BARRERA, FRANCISCO NICOLAS · 2016 to 2020
$1.7M
Optimizing pHLIP: understanding biophysical interactions of membrane insertionR15GM120676 · NIGMS · WEST VIRGINIA UNIVERSITY · PI MERTZ, BLAKE · 2016 to 2016
$414k
NIGMS NIH HHS R01 GM120642NIGMS NIH HHS R15 GM120676
6 · The paper itself

Abstract

The pH-low insertion peptide (pHLIP) is used for targeted delivery of drug cargoes to acidic tissues such as tumors. The extracellular acidosis found in solid tumors triggers pHLIP to transition from a membrane-adsorbed state to fold into a transmembrane α-helix. Different factors influence the acidity required for pHLIP to insert into lipid membranes. One of them is the lipid headgroup composition, which defines the electrostatic profile of the membrane. However, the molecular interactions that drive the adsorption of pHLIP to the bilayer surface are poorly understood. In this study, we combine biophysical experiments and all-atom molecular dynamics simulations to understand the role played by electrostatics in the interaction between pHLIP and a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. We observed that the solution ionic strength affects the structure of pHLIP at the membrane surface as well as the acidity needed for different steps in the membrane insertion process. In particular, our simulations revealed that an increase in ionic strength affected both pHLIP and the bilayer; the coordination of sodium ions with the C-terminus of pHLIP led to localized changes in helicity, whereas the coordination of sodium ions with the phosphate moiety of the phosphocholine headgroups had a condensing effect on our model bilayer. These results are relevant to our understanding of environmental influences on the ability of pHLIP to adsorb to the cell membrane and are useful in our fundamental understanding of the absorption of pH-responsive peptides and cell-penetrating peptides.

Indexed as

IonsMembrane LipidsMembrane ProteinsOsmolar ConcentrationPhosphatidylcholinesProtein Structure, SecondarySodium Chloride1-palmitoyl-2-oleoylphosphatidylcholineIonsMembrane LipidsMembrane ProteinspHLIP proteinPhosphatidylcholinesSodium Chloride

Identifiers

PMID31422821
PMCPMC6731387
OpenAlexW2965756737

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.