Many proteins have been recently shown to undergo a process of phase separation that leads to the formation of biomolecular condensates. Intriguingly, it has been observed that some of these proteins form dense droplets of sizeable dimensions already below the critical concentration, which is the concentration at which phase separation occurs. To understand this phenomenon, which is not readily compatible with classical nucleation theory, we investigated the properties of the droplet size distributions as a function of protein concentration. We found that these distributions can be described by a scale-­invariant log-­normal function with an average that increases progressively as the concentration approaches the critical concentration from below. The results of this scaling analysis suggest the existence of a universal behaviour independent of the sequences and structures of the proteins undergoing phase separation. While we refrain from proposing a theoretical model here, we suggest that any model of protein phase separation should predict the scaling exponents that we reported here from the fitting of experimental measurements of droplet size distributions. Furthermore, based on these observations, we show that it is possible to use the scale invariance to estimate the critical concentration for protein phase separation.

A scale-invariant log-normal droplet size distribution below the critical concentration for protein phase separation

Trovato, Antonio;Fuxreiter, Monika
;
Maritan, Amos
2024

Abstract

Many proteins have been recently shown to undergo a process of phase separation that leads to the formation of biomolecular condensates. Intriguingly, it has been observed that some of these proteins form dense droplets of sizeable dimensions already below the critical concentration, which is the concentration at which phase separation occurs. To understand this phenomenon, which is not readily compatible with classical nucleation theory, we investigated the properties of the droplet size distributions as a function of protein concentration. We found that these distributions can be described by a scale-­invariant log-­normal function with an average that increases progressively as the concentration approaches the critical concentration from below. The results of this scaling analysis suggest the existence of a universal behaviour independent of the sequences and structures of the proteins undergoing phase separation. While we refrain from proposing a theoretical model here, we suggest that any model of protein phase separation should predict the scaling exponents that we reported here from the fitting of experimental measurements of droplet size distributions. Furthermore, based on these observations, we show that it is possible to use the scale invariance to estimate the critical concentration for protein phase separation.
2024
File in questo prodotto:
File Dimensione Formato  
eLife24.pdf

accesso aperto

Descrizione: Main text
Tipologia: Published (Publisher's Version of Record)
Licenza: Creative commons
Dimensione 3.19 MB
Formato Adobe PDF
3.19 MB Adobe PDF Visualizza/Apri
eLife24_mdarchecklist.docx

accesso aperto

Descrizione: MDAR Checklist
Tipologia: Altro materiale allegato
Licenza: Creative commons
Dimensione 88.34 kB
Formato Microsoft Word XML
88.34 kB Microsoft Word XML Visualizza/Apri
eLife24_supp3.xlsx

accesso aperto

Descrizione: Supllementary File 3
Tipologia: Altro materiale allegato
Licenza: Creative commons
Dimensione 28.55 kB
Formato Microsoft Excel XML
28.55 kB Microsoft Excel XML Visualizza/Apri
eLife24_supp2.xlsx

accesso aperto

Descrizione: Supplementary File 2
Tipologia: Altro materiale allegato
Licenza: Creative commons
Dimensione 178.99 kB
Formato Microsoft Excel XML
178.99 kB Microsoft Excel XML Visualizza/Apri
eLife24_supp1.xlsx

accesso aperto

Descrizione: Supplementary FIle 1
Tipologia: Altro materiale allegato
Licenza: Creative commons
Dimensione 28.68 kB
Formato Microsoft Excel XML
28.68 kB Microsoft Excel XML Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3540522
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 4
  • OpenAlex ND
social impact