Lipid News

Progress in identifying lipid domains (rafts) in living cells

Erwin London
By Erwin London
Aug. 1, 2017

Under which conditions lipid chemical heterogeneity results in the formation of coexisting lipid domains with distinct lipid compositions and properties in living cells has been a subject of intense research for decades.

In model membrane formed from lipid mixtures, spontaneous formation of tightly packed sphingolipid- and cholesterol-rich lipid domains (in the liquid-ordered state) that segregate from loosely packed domains richer in unsaturated phospholipids (in the liquid-disordered state) are detected and characterized easily.
lipidraft.png

However, analogous domains in cells are very small under most conditions — at or beyond the limit of detection for most techniques. This has led to much controversy as well as much work aiming to develop new methods to identify and characterize tiny nanodomains.

Very recent progress in living cells has been encouraging on several fronts. Studies using novel fluorescently labeled lipids with affinities for liquid-ordered domains similar to those of unlabeled lipids have revealed that specific association of raft-loving lipids with raft-localizing proteins occurs in living cells (1,2). Single-particle-tracking measurements show that these interactions are lost in living cells when even minor changes in lipid or protein structure are made if these changes abolish raft-associating physical properties.

In other studies, super-resolution microscopy in B cells has found co-localization of raft markers with, and exclusion of nonraft markers from, the vicinity of clustered B-cell receptors on a size scale similar to that of the clusters (50 nanometers to 100 nanometers). This is indicative of the formation of ordered domains around the B-cell receptors. An analogous formation of nanodomains was detected around clustered cholera toxin, a molecule long known to induce the formation of ordered domains in vitro and in cells (3).

These studies extend previous work from other labs that reported lipid-domain-based molecular interactions in these systems. This is indicative of a robust underlying phenomenon.

Advances leading to an increased ability to visualize domains and manipulate their structure promise further progress. An even higher-resolution, super-resolution microscopy approach has been developed, which may allow visualization of domains that otherwise would elude direct visualization (4).

Finally, our own lab has devised a method efficiently to replace virtually the entire complement of plasma membrane outer leaflet lipids in living cells with exogenous lipids. This may allow fine-tuned control of domain formation and properties (5).

REFERENCES

1. Komura, N. et al. Nat. Chem. Biol. 12, 402 – 410 (2016).
2. Kinoshita, M. et al. J. Cell. Biol. 216, 1183 – 1204 (2017).
3. Stone, M.B. et al. eLife 6, e19891 (2017).
4. Balzarotti, F. et al. Science 355, 606 – 612 (2017).
5. Li, G. et al. Proc. Natl. Acad. Sci. USA 113, 14025 – 14030 (2016).

 

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition monthly.

Learn more
Erwin London
Erwin London

Erwin London is a distinguished professor in the department of biochemistry and cell biology and in the department of chemistry at Stony Brook University.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Computational tool helps scientists create novel bug sprays
Journal News

Computational tool helps scientists create novel bug sprays

May 20, 2025

Rapid discovery of mosquito repellent compounds is enabled through a novel screening platform that combines both computational modeling and functional screening.

Meet Lan Huang
Interview

Meet Lan Huang

May 19, 2025

Molecular & Cellular Proteomics associate editor uses crosslinking mass spec to study protein–protein interactions to find novel therapeutics.

Influenza gets help from gum disease bacteria
Journal News

Influenza gets help from gum disease bacteria

May 15, 2025

Scientists discover that a protease from Porphyromonas gingivalis enhances viral spread. Read more about this recent Journal of Biological Chemistry paper.

How bacteria fight back against promising antimicrobial peptide
Journal News

How bacteria fight back against promising antimicrobial peptide

May 15, 2025

Researchers find a mutation in E. coli that reduces its susceptibility to a potential novel antibiotic. Read more about this recent Journal of Biological Chemistry paper.

New clues reveal how cells respond to stress
Journal News

New clues reveal how cells respond to stress

May 15, 2025

Redox signaling protein may help regulate inflammasome and innate immune activation. Read more about this recent Journal of Biological Chemistry paper.

Innovative platform empowers scientists to transform venoms into therapeutics
Journal News

Innovative platform empowers scientists to transform venoms into therapeutics

May 13, 2025

Scientists combine phage display and a “metavenome” library to discover new drugs that bind clinically relevant human cell receptors. Read about this recent Molecular & Cellular Proteomics paper.