Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Membrane Fluidity

Membrane Fluidity

Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...

You might also read

Related Articles

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

Sort by

Same author

Pulse Programme Considerations for Quantitative NOE Analysis.

Magnetic resonance in chemistry : MRC·2026

Same author

What Is in a Structure? Cell Permeability and Solubility of Series of Macrocycles and Linear Matched Pairs.

Journal of medicinal chemistry·2026

Same author

Rural physician deployment programs in five Southeast Asian countries: a policy and narrative review.

BMC health services research·2026

Same author

Field Monitoring of Microplastics in Urban Runoff: Treatment Efficiency of Biofilters.

Environmental science & technology·2026

Same author

Self-Complementary Dimers Based on Zwitterionic Halogen Bond Donors.

Chemistry (Weinheim an der Bergstrasse, Germany)·2026

Same author

Mineralocorticoid Receptor Antagonists With an Acylurea as a Key Polar Interaction Motif.

ChemMedChem·2026

Same journal

Semisynthesis of Mycothiazole Analogs having Distinct Bioactivity.

ACS medicinal chemistry letters·2026

Same journal

Investigation on the Cytotoxicity of Hydroxycinnamic and Hydroxybenzoic Acid-Based Natural Antioxidant Conjugated Terpyridine Analogues toward Triple-Negative Breast Cancer.

ACS medicinal chemistry letters·2026

Same journal

Beyond Neddylation Inhibition: X‑ray Structures Reveal Carbonic Anhydrase Isoform Selectivity of Pevonedistat.

ACS medicinal chemistry letters·2026

Same journal

Structure-Guided Discovery of Selective Polo-Like Kinase 3 Inhibitors.

ACS medicinal chemistry letters·2026

Same journal

Controlling Neuroplasticity Across Scales: Constrained Serotonergic Agonists, Neuroplastogens, and Adaptive Neuromodulation.

ACS medicinal chemistry letters·2026

Same journal

Degradation and Detection: Integrating BCL6 Targeted Protein Degradation with Biomarker-Guided BET Inhibition in Cancer.

ACS medicinal chemistry letters·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Nov 20, 2025

Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy

Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy

Published on: February 17, 2023

Solution Conformations Shed Light on PROTAC Cell Permeability.

Yoseph Atilaw¹, Vasanthanathan Poongavanam¹, Caroline Svensson Nilsson¹

¹Department of Chemistry - BMC, Uppsala University, SE-75123 Uppsala, Sweden.

ACS Medicinal Chemistry Letters

|January 25, 2021

Summary

This summary is machine-generated.

Proteolysis targeting chimeras (PROTACs) can enter cells despite their size. This study reveals PROTACs achieve cell permeability through molecular chameleonicity, adapting their shape and polarity.

More Related Videos

Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution

Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution

Published on: August 16, 2016

A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters

A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters

Published on: April 20, 2015

Related Experiment Videos

Last Updated: Nov 20, 2025

Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy

Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy

Published on: February 17, 2023

Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution

Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution

Published on: August 16, 2016

A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters

A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters

Published on: April 20, 2015

Area of Science:

Medicinal Chemistry
Structural Biology
Drug Discovery

Background:

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules designed for targeted protein degradation.
Their complex chemical structure often presents challenges in achieving favorable ADME properties, including cell permeability.
Understanding the structural basis of PROTAC cell permeability is crucial for advancing drug discovery.

Purpose of the Study:

To provide the first structural insights into the cell permeability of a VHL-based PROTAC.
To elucidate the conformational dynamics of PROTACs in environments mimicking cellular compartments and membranes.
To identify structural features that facilitate PROTAC entry into cells.

Main Methods:

Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study the conformational behavior of a VHL-based PROTAC (compound 1).
Conformational analysis was performed in solutions simulating extracellular, intracellular, and cell membrane interior environments.
Key interactions, such as hydrogen bonds and π-π interactions, were investigated.

Main Results:

Compound 1 demonstrated cell permeability despite its high molecular weight, polarity, and numerous rotatable bonds.
NMR studies revealed that compound 1 adopts elongated, polar conformations in aqueous-like solutions and folded conformations with reduced polar surface area in chloroform.
Intramolecular hydrogen bonds, nonclassical hydrogen bonds, π-π interactions, and shielding of amide groups contribute to minimizing size and polarity for membrane transit.

Conclusions:

Molecular chameleonicity, the ability to adopt different conformations, is critical for the cell permeability of this VHL-based PROTAC.
The findings provide a structural basis for designing PROTACs with improved cell penetration capabilities.
This study highlights the importance of conformational flexibility in overcoming ADME challenges in PROTAC drug discovery.