Universal modulation of liquid-liquid phase separation by macromolecules
- 1Peking University
Abstract
Liquid-liquid phase separation (LLPS) widely organizes the cellular interior, yet how third-party macromolecules modulate LLPS remains a puzzle. While one would expect that macromolecules can either promote or suppress phase separation, empirical observations show that a small dosage of macromolecules virtually always promotes phase separation. To resolve this paradox, we study the linear response of phase separation to macromolecule addition. We prove that for macromolecules significantly larger than the solvent molecule, their addition essentially always promotes phase separation, regardless of how they interact with the scaffold protein. Crucially, in the biologically relevant scenario of dilute condensates, the linear responses, including the saturation volume fraction, scale proportionally to [1-v2(1+{chi}12)2], where v2 is the macromolecule size and {chi}12 is the scaffold-macromolecule interaction parameter. Importantly, this universal behavior extends to multicomponent solutions in which the effective interaction parameter is composition-dependent. Our work shifts macromolecular modulation of LLPS from empirical observation to predictable design.
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BibTeX
@misc{kan2026universal,
title = {{Universal modulation of liquid-liquid phase separation by macromolecules}},
author = {Y. Kan and J. Lin},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749048},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749048v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Universal modulation of liquid-liquid phase separation by macromolecules
AU - Y. Kan
AU - J. Lin
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749048
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749048v1
AB - Liquid-liquid phase separation (LLPS) widely organizes the cellular interior, yet how third-party macromolecules modulate LLPS remains a puzzle. While one would expect that macromolecules can either promote or suppress phase separation, empirical observations show that a small dosage of macromolecules virtually always promotes phase separation. To resolve this paradox, we study the linear response of phase separation to macromolecule addition. We prove that for macromolecules significantly larger than the solvent molecule, their addition essentially always promotes phase separation, regardless of how they interact with the scaffold protein. Crucially, in the biologically relevant scenario of dilute condensates, the linear responses, including the saturation volume fraction, scale proportionally to [1-v2(1+{chi}12)2], where v2 is the macromolecule size and {chi}12 is the scaffold-macromolecule interaction parameter. Importantly, this universal behavior extends to multicomponent solutions in which the effective interaction parameter is composition-dependent. Our work shifts macromolecular modulation of LLPS from empirical observation to predictable design.
ER -