Defining Lineage-Specific Membrane Fluidity Signatures that Regulate Adhesion Kinetics

Cellular membrane fluidity is a critical modulator of cell adhesion and migration, prompting us to define the systematic landscape of lineage-specific cellular fluidity throughout differentiation. Here, we have unveiled membrane fluidity landscapes in various lineages ranging from human pluripotency to differentiated progeny: (1) membrane rigidification precedes the exit from pluripotency, (2) membrane composition modulates activin signaling transmission, and (3) signatures are relatively germ layer specific presumably due to unique lipid compositions. By modulating variable lineage-specific fluidity, we developed a label-free “adhesion sorting (AdSort)” method with simple cultural manipulation, effectively eliminating pluripotent stem cells and purifying target population as a result of the over 1,150 of screened conditions combining compounds and matrices. These results underscore the important role of tunable membrane fluidity in influencing stem cell maintenance and differentiation that can be translated into lineage-specific cell purification strategy. [Display omitted] •Membrane rigidification precedes the exit from pluripotency•Germ layer-specific membrane fluidity signature exists•Identification of polyphenols as a membrane fluidity modulator•Fluidity-based adhesion sorting purify differentiated progeny from pluripotency In this article, Takebe and the colleagues unveiled membrane fluidity landscapes in various lineages ranging from human pluripotency to differentiated progeny. By modulating pluripotent fluidity signature, we developed a label-free “adhesion sorting (AdSort)” method with simple cultural manipulation, effectively eliminating pluripotent stem cells as a result of the over 1,150 of screened conditions combining compounds and matrices.