Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Cellular Membranes and Drug Transport01:24

Cellular Membranes and Drug Transport

245
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
245
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

225
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
225
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

3.0K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport01:23

Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport

329
Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
329
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

3.6K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
3.6K
Single-pass Transmembrane Proteins01:25

Single-pass Transmembrane Proteins

4.8K
Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane...
4.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Overexpression generates aberrant distribution of endocytic regulators - the case of the Rab11/LAMP1 compartment.

PloS one·2026
Same author

HDLs extract lipophilic drugs from cells.

Journal of cell science·2022
Same author

Genetic, cellular, and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore.

eLife·2021
Same author

APOBEC3C, a nucleolar protein induced by genotoxins, is excluded from DNA damage sites.

The FEBS journal·2021
Same author

The proteolytic landscape of cells exposed to non-lethal stresses is shaped by executioner caspases.

Cell death discovery·2021
Same author

Correction to: ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin's lymphoma and testicular cancer cells.

Cell death & disease·2021

Related Experiment Video

Updated: May 17, 2025

Fluorescent Leakage Assay to Investigate Membrane Destabilization by Cell-Penetrating Peptide
07:33

Fluorescent Leakage Assay to Investigate Membrane Destabilization by Cell-Penetrating Peptide

Published on: December 19, 2020

6.2K

No Evidence for Plasma Membrane Potential-Independent Cell Penetrating Peptide Direct Translocation.

Ali Hallaj1, Francisco Tomas Ribeiro1, Christian Widmann1

  • 1Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.

Journal of Peptide Science : an Official Publication of the European Peptide Society
|April 5, 2025
PubMed
Summary

Cell-penetrating peptides (CPPs) require cell membrane hyperpolarization for direct translocation into the cytosol. This finding clarifies previous discrepancies and emphasizes the critical role of membrane potential in CPP uptake.

Keywords:
Plasma membrane potentialcell‐penetrating peptidesdirect translocation

More Related Videos

Measuring Peptide Translocation into Large Unilamellar Vesicles
12:27

Measuring Peptide Translocation into Large Unilamellar Vesicles

Published on: January 27, 2012

13.8K
Engineering Cell-permeable Protein
21:08

Engineering Cell-permeable Protein

Published on: December 28, 2009

14.4K

Related Experiment Videos

Last Updated: May 17, 2025

Fluorescent Leakage Assay to Investigate Membrane Destabilization by Cell-Penetrating Peptide
07:33

Fluorescent Leakage Assay to Investigate Membrane Destabilization by Cell-Penetrating Peptide

Published on: December 19, 2020

6.2K
Measuring Peptide Translocation into Large Unilamellar Vesicles
12:27

Measuring Peptide Translocation into Large Unilamellar Vesicles

Published on: January 27, 2012

13.8K
Engineering Cell-permeable Protein
21:08

Engineering Cell-permeable Protein

Published on: December 28, 2009

14.4K

Area of Science:

  • Cell Biology
  • Biochemistry
  • Membrane Biophysics

Background:

  • Cell-penetrating peptides (CPPs) facilitate cellular entry of cargo molecules.
  • CPPs translocate across the plasma membrane, with mechanisms debated.
  • Previous studies reported conflicting data on the role of membrane potential in CPP uptake.

Purpose of the Study:

  • To investigate the necessity of plasma membrane hyperpolarization for direct CPP translocation.
  • To reconcile discrepant findings regarding CPP uptake mechanisms in different cell lines.

Main Methods:

  • Tested CPP direct translocation across plasma membranes in various cell lines, including HEK and HeLa cells.
  • Manipulated plasma membrane potential (hyperpolarization and depolarization).
  • Analyzed CPP uptake across a range of CPP concentrations.

Main Results:

  • Efficient direct translocation of CPPs consistently requires plasma membrane hyperpolarization.
  • This requirement was observed across all tested cell lines and CPP concentrations.
  • Contradicts previous reports suggesting membrane potential-independent CPP uptake in some cell types.

Conclusions:

  • Plasma membrane hyperpolarization is a critical factor for efficient direct CPP translocation into the cytosol.
  • The study provides a unified explanation for CPP uptake mechanisms, resolving previous discrepancies.
  • Highlights the importance of considering membrane potential in CPP-based drug delivery strategies.