Behind the Science: A Dynamic Model for Cellular Membranes

Behind the Science: A Dynamic Model for Cellular Membranes

Author: Deanne Nolan, Job Boekhoven

Dr. Deanne Nolan, Deputy Editor of ChemSystemsChem, talked to Professor Job Boekhoven, Technical University of Munich, Germany, about his article describing the fuel-driven dissipative self-assembly of dynamic synthetic vesicles. The work is part of a Special Collection on the topic of fuelled self-assembly.

Boekhoven and colleagues have developed a model system for biological membranes in which peptide self-assembly to form dynamic vesicles is driven by a chemical reaction cycle. In this cycle, carbodiimide is used as a chemical fuel and hydrolyzed.

You have designed and synthesized synthetic vesicles as a dynamic model for cellular membranes. Can you tell us a little about the motivation behind this study?

The motivation for this work was to synthesize molecular assemblies that show behavior we typically expect in cells or organisms, but not necessarily in synthetic materials. The life-like behavior we are hunting for is spontaneous emergence, self-division, evolution, and even death. Of course, my dream is to design and synthesize these behaviors in one molecular assembly. Such research could allow the first steps towards synthetic life, but also teach us about the basic requirements for life and its origin.

What were your key findings?

In this work, we developed dynamic vesicles, which is a small step towards the goal of synthetic life. Vesicles, in this context, are assemblies of molecules that are organized in a bilayer membrane which then rolls itself up into a microscopic sphere. It’s kind of like a micro-balloon that spontaneously assembles, and it is crucially important for forming biological compartments like the cell.

Caren Wanzke, the student who developed these dynamic vesicles, coupled a metabolic reaction cycle to the formation of building blocks for these vesicles. The metabolic reaction burns up a chemical fuel, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Once the fuel is burnt, the cycle stops. In other words, once the fuel is used up, building blocks for the vesicles will stop forming, and they will collapse. Indeed, we find that when we add chemical fuel, the vesicles emerge. When the systems run low on fuel, the vesicles decay. Finally, we find that the vesicles, in their short lives, are constantly remodeled, meaning that they rapidly exchange building blocks and constantly change shape.

What are the major differences between typical synthetic lipid membranes and those found in biological systems? How do your dynamic vesicles bridge this gap?

By far, most lipid vesicle models exist in a state close to equilibrium, meaning that they are stable. That is, of course, great as a model system, but it does not reflect well the biological phospholipid vesicles, like the cell wall, which constantly grow, collapse, divide, and remodel. By using our chemically fuelled non-equilibrium process to drive vesicle formation, we aimed to provide a better model.

How critical is the role of the fuel in the assembly process? What drove your choice of EDC as the chemical fuel for this process?

The fuel in our work is what drives the chemical reaction cycle, which, in turn, activates and deactivates building blocks for the vesicles. As a consequence, the number of vesicles, their size, and their dynamics will all be regulated by the rate of the turnover of fuel. I particularly like this EDC-driven reaction cycle because it is simple; it’s predictable, it works. It does not give side products, and with differential equations, we can accurately predict what it is doing in every step in the cycle. The simplicity of the reaction cycle allows us to focus on how it regulates molecular assemblies like the vesicles in this work.

Do you have any plans for future research based on this study?

Our work is the first example in which we can capture this dynamic remodeling of the vesicles driven by chemical energy. I think that’s a huge achievement towards creating synthetic life.

The next step is to direct this dynamic remodeling behavior. For example, after these vesicles emerge, can we force them to catalyze the formation of more vesicle building blocks? Then, we can expect that one vesicle starts catalyzing the formation of others and starts spewing out daughter vesicles. A microscopy movie of such a vesicle is what you can wake me up for any night.

Are there other topics that your research group is interested in?

We are pretty heavily invested in this mission towards synthetic life. My group also focuses on unraveling the mysteries of the origin of life. However, I believe the creation of synthetic life and the study of the origin of life are closely related. It is likely that the molecular mechanisms towards synthetic life also played a role in the origin of life four billion years ago.

Finally, the group is also studying the use of these dynamic molecular assemblies, like the vesicles we discuss in this paper, as materials. We find molecular assemblies in our everyday materials already—for example, you can find vesicles in detergents.

The article they talked about



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