Synthetic cell division: the final cut made possible with a single component

Researchers from the Cees Dekker Lab at Delft University of Technology have shown that Dynamin A proteins, present in bacteria, can constitute a simple machinery capable of giving the final cut during cell division. The DynA machinery represents a step forward towards integration with other processes involved in cell division and therefore towards the assembly of synthetic cells.

Research in bottom-up synthetic biology, i.e. synthetic cells research, aims to shed light on the complex mechanism of life by building functional cells from scratch. These synthetic cells would possess some of the essential functions of their living counterparts, such as the ability to communicate and divide. But cell processes are extremely complex and researchers have to overcome many obstacles along the way.

The research community is therefore adopting a modular approach, trying to develop simplified systems that could reproduce a life process or part of it while being compatible with other systems, with the integration of these systems ultimately leading to functional synthetic cells.

A cell-splitting machinery made from a single component

Nicola De Franceschi

Researchers from the Cees Dekker Lab at Delft University of Technology in the Netherlands have recently shown that a system composed of a single element, the protein dynamin A (DynA), can enable the final cut, i.e. the scission of the cell membrane, the last event in the process of cell division. The results were published in October 2023 in Nature Nanotechnology.

“During cell division, the cell deforms, resulting in the formation of a dumbbell-shaped cell, where a narrow neck still connects the two future daughter cells,” explained Nicola De Franceschi, first author of the paper. “A number of studies have shown that in membrane remodelling processes such as endocytosis1, eukaryotic Dynamin proteins assemble outside the neck and can split the membrane from the outside. But we were looking for a molecular system capable of doing this from the inside.”

Dynamin A proteins are found in bacteria and induce the final stage of spore generation. Using fluorescence microscopy and fluorescence recovery after photobleaching measurements, De Franceschi et al. have provided direct evidence that DynA proteins can induce membrane scission and hemi-scission when reconstituted within the membrane neck of a deformed vesicle. A result that had not previously been demonstrated, and made possible thanks to an approach based on DNA nanotechnology: the synthetic membrane shaper.

Dumbbell in a hemi-scission state. The video shows a dumbbell chain with the two rightmost lobes in a state of hemi-scission. This can be seen by the dimmer fluorescence of the bleached lobe at the end of the video.  Lipid fluorescence is shown in magenta and DynA in green

A synthetic membrane shaper (SMS) to control liposome deformation

In a previous study published in ACS Nano, Nicola De Franceschi and Cees Dekker, in collaboration with researchers from the Dutch BaSyC programme, developed an approach for deforming liposomes, which are artificial vesicles, into specific shapes. Nicola used this approach to remodel liposomes into dumbbells to study the DynA division machinery.

“If the liposomes we used for this study had not been deformed, we would not have been able to obtain these results. The synthetic membrane shaper enabled us to overcome this technical challenge and demonstrate the potential of the DynA division machinery for synthetic cells.”

Dumbbell formation. The video shows the process of deforming the membrane into a dumbbell, captured in real-time using SMS technology.

Future developments

The DynA machinery is a serious contender for achieving synthetic cell division: the system is extremely simple and needs no additional components to position itself at the point where the cell contracts before division, making it possibly more easily integrable than other existing cell-splitting systems.

The road to building synthetic cells still holds many surprises and obstacles in store for researchers. The stage of integration and synchronisation with other modules involved in cell division will represent another challenge: the proteins involved will have to be synthesised from the inside and at the right time, and in the case of the DynA proteins, when the cell deforms and forms a neck.

Read further

Breaking the bottleneck of synthetic cells: In this viewpoint published in Nature Nanotechnology, researcher Oskar Staufer discusses the study by De Franceschi et al. while providing context for readers: the complexity and challenge of assembling synthetic cells, the modular approach adopted by the research community, and why he believes that the simplicity of this division system based on dynamin A brings us closer to synthetic cells capable of dividing and adapting.

Membrane Machines Laboratory: Nicola De Franceschi has since set up his own research group in Warsaw, Poland, where he is further developing the SMS approach to help reconstitute proteins and enable membrane engineering.

Related article: How to achieve cell division in animal cell-like systems

Endocytosis is a cellular process by which the extracellular materials or cargo are transported into intracellular compartments by a series of pathways followed by the formation of vesicles. From: Progress in Molecular Biology and Translational Science, 2023