2020
DOI: 10.1016/j.bpj.2020.07.044
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Liquid Phase Separation Controlled by pH

Abstract: We present a minimal model to study the effects of pH on liquid phase separation of macromolecules. Our model describes a mixture composed of water and macromolecules that exist in three different charge states and have a tendency to phase separate. This phase separation is affected by pH via a set of chemical reactions describing protonation and deprotonation of macromolecules, as well as self-ionization of water. We consider the simple case in which interactions are captured by Flory-Huggins interaction para… Show more

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Cited by 72 publications
(55 citation statements)
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References 45 publications
(65 reference statements)
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“…Next, we sought to generalize the pH-jump approach by demonstrating its rational extension to other proteins. First, we noted that the pH-regulated charge state of a protein is a general determinant of its LLPS 21 , as observed in many cases, such as lysozyme 22 , TDP-43 6 , Sup35 14 , and Pab1 8 . This effect can be rationalized by scrutinizing a typical phase diagram (Fig.…”
Section: Resultsmentioning
confidence: 92%
“…Next, we sought to generalize the pH-jump approach by demonstrating its rational extension to other proteins. First, we noted that the pH-regulated charge state of a protein is a general determinant of its LLPS 21 , as observed in many cases, such as lysozyme 22 , TDP-43 6 , Sup35 14 , and Pab1 8 . This effect can be rationalized by scrutinizing a typical phase diagram (Fig.…”
Section: Resultsmentioning
confidence: 92%
“…In all cases, the spatiotemporal confinement and the resulting population increase in the condensates, increase the concentration from typically low μM in the dilute phase, to high mM-mM concentrations in the dense phase [96][97][98][99][100]. Moreover, the condensates are dynamically formed and sensitive to environmental factors such as phosphorylation, pH and temperature, which can lead to their swift dissolution [101][102][103][104]. Thus, condensate formation may affect specificity in several ways.…”
Section: K Av ¼ [P Bound ]=([P Free ][L])mentioning
confidence: 99%
“…1C). Studies have driven condensate formation using low temperatures, salt concentration, pH, and RNA concentration (Adame‐Arana, Weber, Zaburdaev, Prost, & Julicher, 2020; Kato et al., 2012; Lin, Protter, Rosen, & Parker, 2015; Riback et al., 2020; Sanders et al., 2020; Schwartz, Wang, Podell, & Cech, 2013). Molecular crowding can also be an important driver of phase separation and high‐molecular‐weight sugar polymers like polyethylene glycol and Ficoll can mimic the dense molecular environment within cells (Banani et al., 2017; Kato & McKnight, 2017; Molliex et al., 2015).…”
Section: Introductionmentioning
confidence: 99%