Scientists recreate cellular metabolism within synthetic cells

In living organisms, the cell membrane plays a crucial role. It’s not just a protective barrier—it also senses the environment, helps transport molecules, and allows cells to adapt and change. This flexibility, known as membrane plasticity, comes from a network of chemical reactions fueled by energy. These reactions are part of metabolism, where cells break down and rebuild molecules as needed.

Lipid membranes, built from fatty compounds called phospholipids, are central to this process. Their ability to change shape and composition is critical for growth, repair, and responding to stress. In nature, this remodeling happens thanks to enzymes that constantly build and break down lipids, powered by energy sources like ATP.

For decades, scientists have tried to build synthetic membranes that mimic the functions of real cell membranes. They’ve succeeded in making structures that look like cells but fall short in one key area—metabolism. Without it, artificial membranes are lifeless shells. Now, a team from the University of California San Diego has developed a breakthrough system that gives synthetic membranes a simple metabolic cycle, bringing them one step closer to life.

The research team, led by Neal Devaraj, created an abiotic lipid metabolic network. Instead of relying on living enzymes, they used nonliving chemicals to activate fatty acids. These activated fatty acids then coupled with lysophospholipids to form phospholipids. These molecules self-assembled into membranes, similar to the ones found in cells.

But what makes this system special is that it doesn’t stop at membrane formation. Over time, the phospholipids break back down into their original components. With additional chemical fuel, the process can repeat. This cycle of synthesis and breakdown mimics the metabolism seen in living cells.

To drive this cycle, the researchers used a chemical compound known as an NHS ester. This compound links two lipid tails together but is designed to be unstable. It hydrolyzes in water, meaning the link dissolves over time. When more activating agent is added, the bond reforms, completing the metabolic cycle. This allows the membrane to change and adapt, just like a living cell.

What’s striking is how few ingredients are required. “We are trying to answer the fundamental question: what are the minimal systems that have the properties of life?” said Alessandro Fracassi, the study’s first author and a postdoctoral scholar in Devaraj’s lab. Their system shows that even simple chemistry can produce dynamic behavior—something once thought to be unique to biology.

In natural cells, metabolism lets membranes respond to the environment, grow, and even divide. These processes are needed for evolution and survival. By creating synthetic membranes that can remodel themselves, the researchers are opening a new path to understanding how nonliving matter could have become living.

The team’s work, published in Nature Chemistry, is part of a growing effort to build synthetic cells from the ground up. These cells aren’t meant to replace living ones. Instead, they serve as models for studying life’s origins and testing what’s truly essential for biology.

At some point in Earth’s early history, chemistry crossed a boundary. Nonliving molecules became organized, self-sustaining, and capable of evolution. Scientists still don’t know exactly how this transition happened. But studies like this one offer important clues.

For a long time, efforts to recreate the first steps of life focused on compartments—membranes that separate the inside of a cell from its surroundings. But membranes alone are not enough. Life also needs metabolism: a cycle of building and breaking that keeps cells running.

“Cells that lack a metabolic network are stuck—they aren’t able to remodel, grow or divide,” said Devaraj, who holds the Murray Goodman Endowed Chair in Chemistry and Biochemistry. “Life today is highly evolved, but we want to understand if metabolism can occur in very simple chemical systems, before the evolution of more complex biology occurred.”

This experiment shows it’s possible. By using only abiotic components—chemicals not found in living cells—the researchers recreated a basic version of lipid metabolism. Their system highlights three key features shared by all life: compartmentalization, metabolism, and selection.

Notably, the synthetic membranes demonstrated selection by favoring certain lipid species over others. This kind of self-organization is a foundation for evolution. In future experiments, the team hopes to introduce more complexity, layering functions until a fully functional synthetic cell emerges.

Understanding how life began isn’t just an academic exercise. Artificial cells with dynamic membranes could have many practical uses. These include targeted drug delivery systems, environmentally friendly manufacturing, and advanced biosensors.

“Drug delivery, biomanufacturing, environmental remediation, biomimetic sensors are all possibilities over the coming decades as we continue to deepen our understanding of how life on Earth came to be,” Devaraj said.

Although these applications may take 10 or 20 years to develop, the groundwork being laid today is crucial. Each layer added to synthetic cells—each new behavior—brings us closer to designing systems that can function like life. For now, the team is focused on refining the basic components, ensuring each one performs reliably and predictably.

“We know a lot about living cells and what they’re made of,” said Fracassi. “But if you laid out all the separate components, we don’t actually understand how to put them together to make the cell function as it does. We’re trying to recreate a primitive yet functional cell, one layer at a time.”

Their current results offer a strong foundation. By combining phospholipid synthesis with breakdown and rebuilding, this system captures the essence of biological membranes. It brings synthetic cells closer to acting, adapting, and even evolving—hallmarks of life itself.

Note: The article above provided above by The Brighter Side of News.

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