A Dynamic Model for Cell Membrane Growth in a Genetically Minimal Cell

With 493 genes and 452 protein coding genes the synthetically engineered J. Craig Venter Institute (JCVI) Syn3A Minimal Cell provides a unique platform to study the fundamental processes of a living cell. In addition to determining the production of membrane components (phosphatidylglycerol, glycolipids, transmembrane proteins etc.) required for the cell to double from the expected cell biomass, we have developed a lipid biomass based on lipidomic measurements obtained by the Saenz Research Group (TU-Dresden). After developing these expected "production goals" of the cellular economy, we have constructed a dynamic kinetic model linking lipid metabolism and membrane protein insertion via the Sec system to cell membrane growth utilizing theoretical and experimentally determined values for lipid headgroup membrane surface area contribution. Simulating this model via multi-scale simulation methodologies that we have developed allows us to predict the variation in cell doubling times observed across populations of hundreds of cells, ranging from 90-110 minutes, that are determined by and responsive to other cellular processes such as gene expression and metabolism of key biochemical moieties, such as CTP used in phospholipid synthesis and UTP used in glycolipid synthesis.