Asymmetric cell division is a fundamental process in living systems that underpins cell differentiation, development, and functional diversification. However, due to the lack of intricate spatiotemporal regulation and structural reorganization involved, reproducing this process in artificial cell systems has been highly challenging.

Now, a collaborative team led by Prof. QIAO Yan and WANG Shu, together with scientists from China and the United Kingdom, has developed an innovative strategy for asymmetric division in artificial cells based on transient chemical heterogeneity and interfacial energy gradients.

Their study, published in Nature on May 13, presents a structured droplet-based artificial cell model with autonomous asymmetric division capability. This system enables the spontaneous division of a single parent droplet into two daughter protocells (an inner core droplet and an outer shell vesicle) with distinct morphologies and properties.

The researchers constructed the artificial cell model using lamellar liquid crystalline droplets formed by the self-assembly of lipid molecules and nucleotides. Upon catalysis by alkaline phosphatase, a localized caveola initially emerged on the droplet surface. As the enzymatic reaction progressed, the caveola propagated circumferentially around the droplet, accompanied by the emergence of a distinct shell–core interface within the structure. Once the caveola opening angle exceeded a critical threshold, the inner droplet core was extruded.

At the same time, the detached shell underwent structural relaxation and edge closure. This process ultimately formed a multilamellar vesicular structure that enclosed an internal aqueous lumen. Consequently, the parent droplet divided into two daughter protocells with markedly different structures, compositions, and properties.

These results demonstrated that the enzyme was enriched primarily on the droplet surface, where the dephosphorylation reaction increased the interlamellar spacing of the droplets and induced structural instability within the droplets. Under non-enzymatic conditions, introducing multivalent ions or modulating pH also triggered droplet division.

These findings identified electrostatic shielding as the key driving force for asymmetric division and demonstrated that the division mechanism was broadly applicable, which arises from the synergistic interplay between transient chemical inhomogeneity and interfacial energy gradients. Furthermore, the lamellar liquid crystalline structure and the minor structural defects within the layers were critical for droplet division, whereas structurally disordered droplets underwent only uniform disintegration.

Further studies revealed that the daughter droplets retained enzymatic activity and molecular transport capability. In contrast, the daughter vesicles gradually lost internal organization, released encapsulated molecules, and exhibited a decrease in pH due to ongoing dephosphorylation. These findings suggest that asymmetric division creats distinct chemical microenvironments within the progeny structures, thereby providing a basis for subsequent functional differentiation.

This study offers a new experimental model for understanding the emergence of life-like functions, and lays an important foundation for constructing sophisticated artificial cell systems capable of autonomous proliferation, differentiation, and evolution.