Multiphase organization is a second phase transition within multi-component biomolecular condensates

Abstract

We present a mean-field theoretical model, along with molecular dynamics simulations, to show that the multiphase organization of multi-component condensates is a second phase transition. Whereas the first phase transition that leads to the separation of condensates from the bulk phase is driven by overall attraction among the macromolecular components, the second phase transition can be driven by the disparity in strength between self and cross-species attraction. At a fixed level of disparity in interaction strengths, both of the phase transitions can be observed by decreasing temperature, leading first to the separation of condensates from the bulk phase and then to component demixing inside condensates. The existence of a critical temperature for demixing and predicted binodals are verified by molecular dynamics simulations of model mixtures.

SpiDec: Computing binodals and interfacial tension of biomolecular condensates from simulations of spinodal decomposition

“…We tested the SpiDec method on model systems composed of Lennard-Jones (LJ) particles, LJ chains, hydrophobic-hydrophilic (HP) chains, and patchy particles. The interaction potentials for LJ particles and LJ chains are the same as in our previous studies ( Mazarakos and Zhou, 2021 ; Mazarakos and Zhou, 2022 ). Specifically, the LJ particles interact via the LJ potential, but with a cutoff imposed at , so the actual potential function is shifted to …”

“…Molecular dynamics (MD) simulations then allow the dense and bulk phases to reach equilibration, and the densities of the two phases are then evaluated to build the binodal. This classical slab method has now been applied to a variety of coarse-grained models of biomolecular condensates, from spherical particles and homopolymers (as crude models of structured proteins and IDPs) ( Mazarakos and Zhou, 2021 ; Mazarakos and Zhou, 2022 ) to residue-level models of IDPs ( Das et al, 2018 ; Dignon et al, 2018 ; Statt et al, 2020 ) to multi-bead-per-residue models of dipeptides ( Tang et al, 2021 ). An exciting recent development is the migration of this method to simulations of all-atom models of IDPs in explicit solvent, by first carrying out full simulations at the coarse-grained level and then mapping to atomistic systems ( Zheng et al, 2020 ; Welsh et al, 2022 ).…”

SpiDec: Computing Binodals and Interfacial Tension of Biomolecular Condensates From Simulations of Spinodal Decomposition

“…The interaction potentials for LJ particles and LJ chains are the same as in our previous studies. 9, 25 Specifically, the LJ particles interact via the LJ potential, but with a cutoff imposed at r c = 3 σ , so the actual potential function is shifted to …”

“…The interaction potentials for LJ particles and LJ chains are the same as in our previous studies. 9,25 Specifically, the LJ particles interact via the LJ potential,…”

Coacervation-Induced Remodeling of Nanovesicles

“…We believe such an understanding based on molecular interactions is required to help design novel synthetic polymers to achieve the desired outcome of vesicle remodeling. The use of model systems by a systematic tuning of self- and cross-interaction strengths has been employed to understand the nature of LLPS in the bulk, , but not in the presence of a liposome.…”