The Differentiation of the Plasma Membrane

Abstract

The structure of the plasma membrane is a major determinant of its function, and while recent advances have provided key insights into this relationship, major open questions remain. For example, the diversity of plasma membrane structure and composition in various cell lineages, and the impact of this diversity on cell functions have not been widely explored. Mesenchymal stem cells provide an ideal system to study such changes because they can be directed to undergo differentiation along several lineages (e.g. adipocyte, osteocyte) within a short timeframe (~2 weeks) and with minimal biochemical perturbations. Giant Plasma Membrane Vesicles isolated from the various lineages allow for simultaneous quantification of plasma membrane order, composition, and liquid‐liquid separation into raft and non‐raft domains. We find striking differences in phase separation and overall membrane packing between different cell lineages and correlate them to the differentiation of the plasma membrane lipidomes measured by quantitative, comprehensive shotgun mass spectrometry. In addition to being the first to compare plasma membrane properties and compositions during differentiation, these observations also enable identification of the compositional determinants of the physical properties of biological membranes.