Shape-shifting vesicles mimic living cells .

Microscopic vesicles that swirl with oscillating surface patterns and sprout appendages like living cells have been unveiled by an international team of scientists. The researchers say that the tiny objects could be an important step in the development of shape-changing soft materials and may even shed light on some biological processes.

The vesicles were created using lipid bilayers and other components found in living cells. The work was done by scientists at Technische Universität München (TUM) in Germany, Brandeis University and Syracuse University in the US, SISSA International School for Advanced Studies in Italy, and Leiden University in the Netherlands

The shape shifting is achieved by creating an artificial cytoskeleton, which is the dynamic structure of microtubules found within living cells. “Here, we managed for the first time to reconstitute a part of the cytoskeleton inside a vesicle – in an active state, which means forces are exerted continuously inside the vesicle, leading to deformations and shape transformations of the vesicle,” Andreas Bausch, a researcher at TUM and team leader,

Motors and scaffolding

The team formed lipid-bilayer vesicles tens of microns in diameter, and gave them an inner lining of microtubules. The researchers also added kinesin molecular motors, bound together in clusters, which formed cross-links among the microtubules. The resulting bundles of microtubules attached themselves to the inner surface of each vesicle as a nematic film – a single layer of parallel molecules with the fluid and self-assembly properties of a liquid crystal.

As in previous studies of nematic fluids on spherical surfaces, the flat sheets of parallel-aligning molecules had to bend to conform to the round surface. As a result, defects similar to the loops seen in fingerprints formed among the parallel lines. As the attractive forces in the film achieved equilibrium, the defects migrated apart and became stable at equal distances from one another. A typical number of singularities for a sphere was four, which stopped in positions at the points of an imaginary tetrahedron within the vesicle.

However, the kinesin motors ensured that the defects did not stay in place for long. Clusters of molecular motors latched onto adjacent microtubules and pulled them in opposite directions, forcing the long molecules to slide lengthwise past each other. This continuous action maintained a steady outward push, forcing each bundle to keep lengthening.

Migrating singularities

Pushed out of their stable tetrahedral points, the singularities migrated to new positions, passing through an orientation with all four in the same plane before settling again into a new tetrahedron. The motion continues as the singularities are forced out of those positions and begin another oscillation.

By creating an osmotic gradient between the inside and outside of the vesicles, the researchers could create arm-like protrusions that resemble the filopodia that occur in some living cells. As osmotic pressure deflated a vesicle, a surplus of membrane became available. In the defects, microtubules quickly took up this extra membrane as they aligned in parallel and extended outward as new appendages. When the osmotic pressure was reversed, the swelling vesicle reclaimed the surplus membrane, retracting the appendages.

“To me, it’s very cool; it’s dynamism,” says David Nelson of Harvard University. Nelson explains that all previous studies of nematic films on round surfaces focused on films in equilibrium. Defects had formed but had not moved, and no one had engineered a vesicle that grew filopodia-like appendages. “They made these defects come alive,” he says.

Hand-drawn noodles

Randall Kamien of the University of Pennsylvania points out three areas of significance. “First of all, this demonstrates that topological constraints that control equilibrium behaviour react much, much differently out of equilibrium,” he says. “Secondly [citing a figure in the paper describing the work], the beautiful mode that looks like how hand-drawn noodles are made suggests that this mechanism could be used for mixing on the few-micron level. Finally, the oscillation frequency of these states is about once per hundred seconds. Cell cycles are typically much longer. What role could oscillators at this time scale do in vivo? Are they present in cells?”

Bausch and his colleagues are focusing on future insights into basic biology. “[We want to] rebuild biological complexity by a bottom-up approach,” he says. “The big goal – very, very long term – is to rebuild cellular functions like cell migration or cell division. This is only a first step.”

Vincenzo Vitelli of Leiden University also believes that the research could improve our understanding of biology. “These synthetic structures are close enough to living organisms to provide insights into the behaviour of early life forms that marked the cross-over from inanimate to living matter,” says Vitelli, who was not involved with the research.

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