Lipid flip flop regulates the shape of growing and dividing synthetic cells

Cells grow their boundaries by incorporating newly synthesized lipids into their membranes as well as through fusion of intracellular vesicles. As these processes yield trans-bilayer imbalances in lipid numbers, cells must actively flip lipid molecules across the bilayer to enable growth. Using giant and small unilamellar vesicles (GUVs and SUVs, respectively), we here recapitulate cellular growth and division under various conditions of transmembrane flip flop of lipids. By dynamically monitoring the changes in reduced volume and spontaneous curvature of GUVs that grow by fusion of many small SUVs, the morphology of these growing synthetic cells is quantified. We demonstrate that lipid flip flop relaxes curvature stresses and yields more symmetrically sized buds. Further increasing the neck curvature is shown to lead to bud scission. The mechanisms presented here offer fundamental insights into cell growth and division, which are important for understanding early protocells and designing synthetic cells that are able to grow and divide.