Actin (green) forms long, tube-like structures in the cell.

Actin (green) forms long, tube-like structures in the cell.

iStock/Beano5

Researchers use actin to develop synthetic condensates

Cell membranes act as containers for cell contents. Synthetic cells need them too. Researchers developed a new vessel that uses an unusual border: actin.
Natalya Ortolano, PhD Headshot
| 3 min read
Register for free to listen to this article
Listen with Speechify
0:00
3:00

Through the lens of a microscope, cells look like they are filled with tiny, indistinct bubbles. But these bubbles are more than meets the eye. These liquid-like aggregations are clusters of proteins and macromolecules called biomolecular condensates, and they are critical for everyday function.

Researchers noted membraneless condensates in the early 1900s, but their role in cell function and disease was overlooked until the last decade. A group of researchers from Wageningen University and Research reported in a recent preprint article that they leveraged the power of condensates to fine tune some newcomers to the research scene: synthetic cells (1).

Synthetic cells are biologically engineered containers carrying proteins and nucleotides that work together to perform basic cellular functions, such as transport and energy production. Synthetic cells allow scientists to recapitulate cellular processes in a controlled setting. They also have the potential to act as a drug delivery system, shuttling drugs to a specific part of the body and releasing them based on a particular cue.

The key to a good synthetic cell is its container. Some researchers wrap the contents in a lipid-like membrane or engineered proteins, while others take a membrane-free approach, using engineered or synthetic material to form condensates. The researchers from Wageningen University and Research added a new twist for membraneless containers.

“There have been efforts to make artificial [membraneless] compartments, but these efforts were based on older chemistry,” said Kate Adamala, co-founder of Build-A-Cell and a synthetic cell builder at the University of Minnesota. “This paper is super clever because it uses a natural property of a really common, well-known, well-studied protein called actin. They use actin as a shell to create a compartment. It’s kind of elegant because it uses something every organism has.”

Actin is a protein that forms long, string-like, flexible filaments with other actin molecules. It acts like a scaffold in the cell, making it an attractive option as a container component for a synthetic membraneless cell. But that’s not why synthetic biologist Siddharth Deshpande, the senior author of the recent preprint, focused on it.

“We are interested in studying actin-condensate interactions,” said Deshpande. “We wanted to do this in an in vitro fashion in a controlled way. In one of the negative controls, we saw that when we mixed GTP and ATP in the condensate, we actually got something like a container.”

Desphande’s group makes actin-coated (green) condensates, precursors to actinosomes.
CREDIT: SIDDHARTH DESHPANDE

Deshpande’s group first created condensates containing ATP, GTP, and amino acid polypeptides. When they incorporated actin, the protein coated the outside of the condensate. They then triggered actin polymerization by adding ATP, which fueled the formation of long actin filaments from the actin monomers. These actin fibers transformed the small condensate into a more structured container supported by actin filaments, a structure Deshpande coined an actinosome. Akin to cells, their actinosomes could express a GFP-tagged protein from an RNA template.

“We can really easily make these containers,” said Deshpande. “We can make it in a tube by adding the solutions and vortexing it.” 

Adamala is excited to see how Deshpande’s team builds on this work as they prepare it for publication.

“It would be really interesting to see if those compartments can form as you’re expressing actin [in the condensates]. That would make it really powerful,” said Adamala.

Deshpande is still fine-tuning the actinosomes and testing their capabilities as synthetic cell containers, but he thinks that they might provide an easy-to-make and use compartment for synthetic cell applications.

“Synthetic cells definitely have a very high potential for drug delivery. If you can make a smart container that can deliver the drug of your choice to the target of your choice, that will be amazing. At the same time, you want your container to be biocompatible, and actin is, of course, highly biocompatible,” said Deshpande.

Reference

Ganar K. A. et al. Actinosomes: condensate-templated proteinaceous containers for engineering synthetic cells. bioRxiv (2021).

About the Author

  • Natalya Ortolano, PhD Headshot

    Natalya received her PhD in from Vanderbilt University in 2021; she joined the DDN team the same week she defended her thesis. Her work has been featured at STAT News, Vanderbilt Magazine, and Scientific American. As an assistant editor, she writes and edits online and print stories on topics ranging from cows to psychedelics. Outside of work you can probably find her at a concert in her hometown Nashville, TN.

Related Topics

Published In

February 2022 | Volume 18 | Issue 2 | Front Cover
Volume 18 - Issue 2 | February 2022

February 2022

February 2022 Issue

Loading Next Article...
Loading Next Article...
Subscribe to Newsletter

Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

Subscribe

Sponsored

A black mosquito is shown on pink human skin against a blurred green backdrop.

Discovering deeper insights into malaria research

Malaria continues to drive urgent research worldwide, with new therapies and tools emerging to combat the parasite’s complex lifecycle and global burden.
Three burgundy round and linear conformations of oligonucleotides are shown against a black background.

Accelerating RNA therapeutic testing with liver microphysiological platforms

Researchers can now study oligonucleotide delivery and efficacy in a system that models a real human liver.
A 3D-rendered illustration of a eukaryotic cell highlighting organelles such as the nucleus, endoplasmic reticulum, mitochondria, and cytoskeletal structures in pink and purple tones.

Shining light on the subcellular proteome

Discover how innovative proteomics tools help researchers peer into once inaccessible organelles, allowing for new targets for drug discovery and development.
Drug Discovery News March 2025 Issue
Latest IssueVolume 21 • Issue 1 • March 2025

March 2025

March 2025 Issue

Explore this issue