A photoswitchable biosystem for the development of synthetic cells could provide a noninvasive way to design intelligent drug delivery systems for cell repair, advancing applications in photopharmacology. A team from the Max Planck Institute of Colloids and Interfaces, led by researcher Rumiana Dimova, demonstrated that interactions between a synthetic cell membrane and glycinin protein condensates integrated in the cell can be manipulated with light, and that such modulation can lead to endocytosis of the condensates. To replicate endocytosis — the process by which a cell wraps its outer membrane around nutrients or pathogens to ingest them — the researchers constructed cell-sized, biomimetic membrane platforms known as giant unilamellar vesicles (GUVs). They introduced photoswitchable lipids into the GUVs. The researchers used the GUVs to simulate cellular processes, including interactions with protein condensates, and analyzed the processes using confocal microscopy. Researchers Agustin Mangiarotti and Mina Aleksanyan record the membrane response at the confocal microscope. Courtesy of Max Planck Institute of Colloids and Interfaces. By shining light of different colors on the GUVs, the researchers were able to manipulate the interactions between the GUVs and condensates. The light caused the GUVs to change in size and triggered various interactions between the cellular components. UV light was found to activate endocytosis. “When we shine ultraviolet light on a membrane, it grows and swallows the condensates,” researcher Agustín Mangiarotti said. Blue light, in contrast, reversed the endocytosis process by causing the membrane to shrink, expelling the condensate, said researcher Mina Aleksanyan. The researchers used confocal microscopy to quantify the affinity of the protein condensates to the GUV membrane and the reversibility of the endocytosis process. They found that the degree of photo-induced endocytosis, whether partial or complete, depended on the excess area of the GUV and the relative sizes of GUVs and condensates. The light-induced transitions led to fast, reversible endocytosis, occurring within a few seconds, over multiple photoswitching cycles. Bio-inspired, photolipid-doped cell models and liposomal drug carriers, when manipulated with light, could offer noninvasive therapeutic applications to address cellular disorders. Light is inexpensive and sustainable, making it a practical tool for manipulating cellular dynamics. Because GUVs are synthesized in a lab environment, the use of GUVs for research eliminates the need for researchers to acquire cell cultures from living organisms to probe cellular processes. Biomimetic GUVs are made from molecules found in the human body, like fats and proteins. As such, they can serve as tiny capsules to carry drugs into the body and can fuse organically with the body’s cells. By controlling and tuning the interactions between GUVs and condensates with light, it could be possible to deliver specific drugs directly into the cells, adjust the delivery, and if needed, reverse it. “Now we know that by modulating light we can control how vesicles shape the inner environment of a cell, which could help treat cellular disorders,” Dimova said. “It’s like being able to sculpt a cell from the inside by flicking a light switch.” The research was published in Advanced Science (www.doi.org/10.1002/advs.202309864).