Rich Phase Separation Behavior of Biomolecules

Abstract

Phase separation is a thermodynamic process leading to the formation of compositionally distinct phases. For the past few years, numerous works have shown that biomolecular phase separation serves as biogenesis mechanisms of diverse intracellular condensates, and aberrant phase transitions are associated with disease states such as neurodegenerative diseases and cancers. Condensates exhibit rich phase behaviors including multiphase internal structuring, noise buffering, and compositional tunability. Recent studies have begun to uncover how a network of intermolecular interactions can give rise to various biophysical features of condensates. Here, we review phase behaviors of biomolecules, particularly with regard to regular solution models of binary and ternary mixtures. We discuss how these theoretical frameworks explain many aspects of the assembly, composition, and miscibility of diverse biomolecular phases, and highlight how a model-based approach can help elucidate the detailed thermodynamic principle for multicomponent intracellular phase separation.

Liquid-Liquid Phase Separation of DDR1 Counteracts the Hippo Pathway to Orchestrate Arterial Stiffening

“…53 Aberrant phase separation was demonstrated as a contributing factor to the pathogenesis of neurodegenerative diseases and cancer. 34,35 However, the roles of LLPS in cardiovascular diseases remain poorly understood. Here, we reported that the mechanoreceptive protein DDR1 is capable of undergoing LLPS in response to collagen binding or ECM stiffness.…”

“…32,33 Recently, LLPS was indicated to play a vital role in human health and diseases. 34,35 There is little information as to how LLPS is involved in vascular physiology and pathophysiology. Here, we describe an LLPS-dependent mechanism of DDR1 mediating Hippo-dependent YAP activation in response to the mechanical and chemical stimuli.…”

Phase separation in cancer at a glance

“…LLPS occurs within cells as macromolecules transition between dense and diluted phases, which is necessary for achieving the lowest free energy state [ 10 ]. A characteristic of LLPS is the presence of threshold concentrations of macromolecules, which are affected by several biophysical parameters, including temperature, salt concentration, and ions [ 6 ].…”

Phase separation drives the formation of biomolecular condensates in the immune system

“…Like the liquid phase, when the temperature changes, it may separate into two immiscible liquid phases, or into a solid phase and a liquid phase. LLPS refers to the phenomenon in which two mixed liquids are separated from each other ( 38 – 40 ). Phase separation can be coupled with various other phase transitions in the complex environment in vivo , which physically range from non-viscous (like water at room temperature) to gel-like.…”