Thermodynamically driven assemblies and liquid–liquid phase separations in biology

Abstract

The sustenance of life depends on the high degree of organization that prevails through different levels of living organisms, from subcellular structures such as biomolecular complexes and organelles to tissues and organs. The physical origin of such organization is not fully understood, and even though it is clear that cells and organisms cannot maintain their integrity without consuming energy, there is growing evidence that individual assembly processes can be thermodynamically driven and occur spontaneously due to changes in thermodynamic variables such as intermolecular interactions and concentration. Understanding the phase separation in vivo requires a multidisciplinary approach, integrating the theory and physics of phase separation with experimental and computational techniques. This paper aims at providing a brief overview of the physics of phase separation and its biological implications, with a particular focus on the assembly of membraneless organelles. We discuss the underlying physical principles of phase separation from its thermodynamics to its kinetics. We also overview the wide range of methods utilized for experimental verification and characterization of phase separation of membraneless organelles, as well as the utility of molecular simulations rooted in thermodynamics and statistical physics in understanding the governing principles of thermodynamically driven biological self-assembly processes.arXiv:1812.09412v1 [cond-mat.soft]

Temperature, Hydrostatic Pressure, and Osmolyte Effects on Liquid–Liquid Phase Separation in Protein Condensates: Physical Chemistry and Biological Implications

“…(b) LLPS exhibits either lower-critical solutiont emperature (LCST) and/or upper-criticals olution temperature( UCST) phase behavior (*:critical points).D epending on the balance between solvent-mediatedprotein-protein interactions and protein configurationale ntropy, [31][32][33] the LLPS region with aL CSTmight also have an UCST,t hat is, the coexistence and spinodalc urves might close at ah ighert emperature(such as cenario is likely for certain elastinlikepeptides), [34] as noted by Schneider [35] and discussedr ecently in the context of biomolecularcondensates. [36,37] For compositionsw ithin the spinodal region (above the spinodalc urve for systems with aL CST,below the spinodal curve for systemsw ith an UCST), small fluctuationsi nc omposition lead to spontaneous phase separation via spinodal decomposition. Betweent he coexistence (binodal) and spinodal curves is the nucleation regimei nwhich the homogeneoussolution phase is metastable with respect to fluctuations.…”

“…As the thermodynamics of temperature-dependent biomolecular LLPS has been well covered in recent papers and reviews (see refs. [32,33,[36][37][38]79]), the attention of this sectioni s largely restricted to the pressure aspects of the basic thermodynamics relevant to LLPS phenomena in the temperaturepressure phase space. [35,[80][81][82] When al iquid mixture is subjected to pressure, the critical solution temperature T c changes.…”

The involvement of stress granules in aging and aging‐associated diseases

“…This can lead the LLPS‐derived liquid assembly to take on gel‐like or solid‐like properties, which may not function properly (Alberti & Dormann, 2019). Such pathological assemblies, induced by LLPS, are involved in the onset of diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and Parkinson's disease (Alberti & Dormann, 2019; Falahati & Haji‐Akbari, 2019). The molecules that undergo phase separation include proteins composed of modular interaction domains and intrinsically disordered regions (IDRs).…”

Protein phase separation and determinants of in cell crystallization

“…To date it remains challenging to investigate in cell phase separation phenomena on a molecular level . Therefore, several investigations on LLPS and biomolecular condensates are currently performed applying well‐defined in vitro systems using selected proteins and distinct crowding agents .…”