RT Journal Article SR Electronic T1 Kinetic frustration by limited bond availability controls the LAT protein condensation phase transition on membranes JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.12.05.471009 DO 10.1101/2021.12.05.471009 A1 Simou Sun A1 Trevor GrandPre A1 David T. Limmer A1 Jay T. Groves YR 2021 UL http://biorxiv.org/content/early/2021/12/06/2021.12.05.471009.abstract AB LAT is a membrane-linked scaffold protein that undergoes a phase transition to form a two-dimensional protein condensate on the membrane during T cell activation. Governed by tyrosine phosphorylation, LAT recruits various proteins that ultimately enable condensation through a percolation network of discrete and selective protein-protein interactions. Here we describe detailed kinetic measurements of the phase transition, along with coarse-grained model simulations, that reveal LAT condensation is kinetically frustrated by the availability of bonds to form the network. Unlike typical miscibility transitions in which compact domains may coexist at equilibrium, the LAT condensates are dynamically arrested in extended states, kinetically trapped out of equilibrium. Modeling identifies the structural basis for this kinetic arrest as the formation of spindle arrangements, favored by limited multivalent binding interactions along the flexible, intrinsically disordered LAT protein. These results reveal how local factors controlling the kinetics of LAT condensation enable formation of different, stable condensates, which may ultimately coexist within the cell.Competing Interest StatementThe authors have declared no competing interest.