#Entropy chemistry driver#
#Entropy chemistry free#

The question we ask is what are the driving forces for CC between oppositely charged polyelectrolytes? What is the minimum requirement to establish LCST (or UCST) behavior in CC? The CC between polyelectrolytes with minimal sequence complexity and hydrophobicity compared to protein will teach us about the base property of CC, especially under conditions that mimic the cellular environment. However, it is important to note that both counterion-release and dehydration entropy would be greater at lower ionic strength where the effective surface charge of the polyelectrolytes is greater. In a study by Van der Gucht, counterion-release entropy was found to be most negative at the lowest ionic strength 37.

#Entropy chemistry driver#

However, a recent study relying on experimental and field-theoretic simulations (FTS) of CC between the IDP tau and RNA demonstrated that counterion-release to be a negligible driver of CC, or at least does not need to be invoked to replicate LCST-driven CC 22, while hydration water-release may be a major contributor to entropy gain. The origin of the entropy gain is assumed in the literature to be due to counterion-release 35, 36, 37, 38. For many CC processes О” H CC is a small value, but the entropy gain may be positive (О” S CCвЂ‰>вЂ‰0), in which case lower critical solution temperature (LCST) behavior is observed, where increasing temperature favors LLPS 18, 22, 34.

#Entropy chemistry free#

Thus, the above-listed factors all contribute to modulating the free energy for CC formation (О” G CC), where CC will occur when О” G CC (=О” H CCвЂ‰в€’ TО” S CC) is negative. It is by now firmly established that CC, fundamentally and without specific biological driving factors, is an equilibrium state that can be described by a phase diagram 22, 31, 32, 33. Complex coacervation is affected by many factors including ionic strength, pH, polyelectrolyte concentration, a balanced mixing ratio of oppositely charged polyelectrolytes, molecular weight of the polyelectrolytes, as well as temperature and the crowding pressure 30. Interactions other than electrostatic interactions have also been shown to modulate or even drive LLPS, including by cation-ПЂ 27 or hydrophobic interaction 28, 29. Coacervation can also occur by an inter-molecular association of a single component, known as simple coacervation 24, 25, 26. CC typically occurs when oppositely charged polyelectrolytes (referring to either the entire biopolymer or a biopolymer segment) interact with each other by electrostatic attraction, and ultimately form polyelectrolyte microdroplets termed the complex coacervate phase. If LLPS with IDPs is to be a regulatory state of importance to cellular processes, it makes sense that its formation and dissolution conditions be modulated by physiological relevant factors within crowded environments 22.Д¬omplex coacervation is a phenomenon in which polyelectrolytes separate into a polyelectrolyte-rich phase (dense phase) and a polyelectrolyte-depleted phase (dilute phase) 23. Given that CC represents one of the most robust mechanisms to drive LLPS, it has been used as a model system to investigate whether their formation involving IDPs correlate with human disease conditions 17, 18, 19, 20, 21.

This is because coacervate can be composed of simple components, while they are capable of taking up various substances and segregate from the environment. Historically, complex coacervation (CC), which results in LLPS, has been suggested to share the genesis of the protocell 15, 16. There are examples in the literature of membraneless organelles found in living cells 10, 13, 14. Interestingly, some membraneless organelles composed of IDPs have displayed liquid-like physical properties 9, 10, 11, 12, suggesting that intracellular droplet formation by liquidв€’liquid phase separation (LLPS) may be a relevant mechanism for the formation of membraneless organelles. Recent research has provided clues that IDPs play a key role in protein regulation inside cells 3, 4, 5, as well as participate in the formation of membraneless organelles 6, 7, 8. Around 50% of the protein sequence with segment length >30 amino acids coded by the human genome are predicted to be intrinsically disordered proteins (IDPs) without a three-dimensional structure 1, 2.