The field of synthetic biology is growing rapidly, with researchers constantly pushing the possible boundaries of what can be created. One area of particular interest is the creation of artificial cells, also known as protocells. These are microscopic structures that mimic some of the functions of biological cells and have the potential to be used for a variety of applications, such as drug delivery, biosensing, and even regenerative medicine.
However, one of the major challenges in creating artificial cells is that they often lack a key component: the cytoskeleton. The cytoskeleton is a network of filaments that provides structure and support to cells, and it also plays a critical role in cell movement, division, and transport of materials within the cell. Without a cytoskeleton, artificial cells are essentially bags of chemicals and lack the functionality and sophistication of natural cells.
In a recent breakthrough study published in Nature, researchers have devised a novel approach to design artificial cells with a synthetic cytoskeleton. Their work represents a significant step forward in the field of synthetic biology and has the potential to pave the way for the creation of more complex and functional artificial cells.
Artificial cells Actin-Binding Proteins
The natural cytoskeleton is composed of actin filaments, which are long, thin protein fibers. These filaments are crosslinked and bundled together by various proteins, including actin-binding proteins. These proteins play a crucial role in determining the shape, mechanics, and dynamics of the cytoskeleton.
In this study, the researchers aimed to mimic the function of actin-binding proteins using synthetic molecules. They achieved this by designing peptide-DNA crosslinkers. Peptides are short chains of amino acids, the building blocks of proteins. DNA, on the other hand, is the genetic material that encodes the instructions for building proteins.
The researchers cleverly designed their peptide-DNA crosslinkers to have two key functionalities. First, the peptide portion was designed to bind specifically to actin filaments. Second, the DNA portion was designed to self-assemble and form double-stranded structures. This self-assembly property allowed the crosslinkers to bridge multiple actin filaments, effectively mimicking the function of natural actin-binding proteins.
Artificial Cells Function with Synthetic Cytoskeleton
One of the most exciting aspects of this study is the ability to control the shape and function of artificial cells by varying the design of the peptide-DNA crosslinkers. The researchers found that they could manipulate the following properties of the crosslinkers:
- Length: By changing the length of the crosslinker, the researchers could control the distance between crosslinked actin filaments. This in turn affected the overall mesh size of the synthetic cytoskeleton.
- Valency: The valency refers to the number of actin filaments that a single crosslinker can bind to. By varying the valency of the crosslinker, the researchers could control the degree of crosslinking within the synthetic cytoskeleton.
- Geometry: The geometry of the crosslinker refers to its three-dimensional structure. The researchers explored crosslinkers with different geometries and found that this could influence the organization and dynamics of the synthetic cytoskeleton.
By fine-tuning these properties, the researchers were able to create synthetic cells with a variety of shapes and functionalities. For example, they could create cells that were more spherical or more elongated. They could also create cells that were better at transporting materials within the cell, mimicking the role of the natural cytoskeleton in intracellular transport.
Implications for the Future of Synthetic Biology
The development of synthetic cytoskeletons represents a major leap forward in the field of synthetic biology. This approach provides researchers with a powerful tool for engineering artificial cells with specific functionalities. This has the potential to open up a wide range of new applications, including:
- Drug Delivery: Artificial cells with synthetic cytoskeletons could be designed to deliver drugs to specific targets within the body. The ability to control the shape and transport properties of these cells could allow for more targeted and efficient drug delivery.
- Biosensing: Artificial cells could be engineered to sense specific molecules or environmental changes. The synthetic cytoskeleton could be used to design these cells to respond to these stimuli in a controlled manner, making them ideal for biosensing applications.
- Regenerative Medicine: Synthetic cells with cytoskeletons could potentially be used to regenerate damaged tissues. By mimicking the structure and function of natural cells, these artificial cells could provide a novel approach to tissue repair and regeneration.
The design of synthetic cytoskeletons for artificial cells represents a significant milestone in the field of synthetic biology. This work opens up new avenues for the creation of more complex and functional
Source:
Margaret L. Daly, Kengo Nishi, Stephen J. Klawa, Kameryn Y. Hinton, Yuan Gao, Ronit Freeman. Designer peptide–DNA cytoskeletons regulate the function of synthetic cells. Nature Chemistry, 2024; DOI: 10.1038/s41557-024-01509-w
A molecular biologist and aspiring bioinformatician with a passion for genomics, rare diseases, and precision medicine. With an MPhil in Molecular Biology and experience in genetics and genomics, he has contributed to clinical research projects on rare genetic disorders. He’s passionate about making genomic data meaningful — and ultimately helpful — for patients and clinicians alike.