Revolutionizing Synthetic Biology: DNA Nanobots Redefine Artificial Cell Design

The form and structure of a cell are crucial for its biological role. This relates to the guideline of “form follows function,” a principle prevalent in contemporary design and architecture fields. Applying this concept to artificial cells presents a challenge in synthetic biology. Recent advancements in DNA nanotechnology provide hopeful alternatives. These innovations facilitate the construction of new transport channels that are sufficiently large to allow therapeutic proteins to traverse cell membranes.

In this developing field, Prof. Laura Na Liu, Director of the 2nd Physics Institute at the University of Stuttgart and Fellow at the Max Planck Institute for Solid State Research (MPI-FKF), has conceived a groundbreaking instrument for managing the shape and permeability of lipid membranes within synthetic cells. These membranes, composed of lipid bilayers encasing an aqueous chamber, serve as simplified representations of biological membranes. They are advantageous for examining membrane dynamics, protein interactions, and lipid behaviors.

The research is published in Nature Materials.

A breakthrough in the implementation of DNA nanotechnology

This innovative tool could lead to the development of functional synthetic cells. Laura Na Liu’s work aspires to make a significant impact on the exploration and creation of new therapies. Liu and her team have successfully employed signal-dependent DNA nanorobots to facilitate programmable interactions with synthetic cells.

“This research marks a significant advancement in utilizing DNA nanotechnology to govern cell behaviors,” Liu states.

The team engages with giant unilamellar vesicles (GUVs), which are straightforward, cell-like structures that simulate living cells. Through the use of DNA nanorobots, the scientists were capable of altering the shape and functionality of these synthetic cells.

New transport pathways for proteins and enzymes

DNA nanotechnology constitutes one of Laura Na Liu’s principal research domains. She specializes in DNA origami formations—DNA strands meticulously folded using specifically devised shorter DNA sequences known as staples. Liu’s team employed DNA origami configurations as reconfigurable nanorobots that can reversibly change their form, thus impacting their surrounding environment at the micrometer scale.

The researchers discovered that the transformation of these DNA nanorobots could be linked with the distortion of the GUVs and the creation of synthetic channels within the model GUV membranes. These channels enabled the passage of large molecules through the membrane and can be resealed if necessary.

Completely artificial DNA configurations for biological settings

“This indicates that we can employ DNA nanorobots to design the shape and configuration of GUVs to facilitate the establishment of transport channels in the membrane,” remarks Prof. Stephan Nussberger, a co-author of this research.

“It is incredibly exciting that the operational mechanism of the DNA nanorobots on GUVs has no direct biological equivalent in living organisms.”

The recent research brings forth new inquiries: Is it possible to engineer synthetic platforms—such as DNA nanorobots—with fewer complexities than their biological counterparts, yet still function within a biological environment?

Comprehending disease mechanisms and enhancing treatments

The recent research represents a pivotal advancement in this area. The network of cross-membrane channels, engineered by DNA nanobots, enables effective transfer of specific molecules and compounds into the cells. Most notably, these channels are sizable and can be programmed to seal when necessary.

When utilized on living cells, this system can streamline the delivery of therapeutic proteins or enzymes to their intended destinations within the cell. Consequently, it presents new avenues for drug delivery and other therapeutic measures.

“Our method unveils new opportunities to replicate the functions of living cells. This advancement could be vital for upcoming therapeutic approaches,” states Prof. Hao Yan, a co-author of this research.