Details

Autor(en) / Beteiligte

• Shillcock, Julian C
• Lagisquet, Clément
• Alexandre, Jérémy
• Vuillon, Laurent
• Ipsen, John H

Titel

Model biomolecular condensates have heterogeneous structure quantitatively dependent on the interaction profile of their constituent macromolecules

Ist Teil von

• Soft matter, 2022-09, Vol.18 (35), p.6674-6693

Ort / Verlag

Cambridge: Royal Society of Chemistry

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Biomolecular condensates play numerous roles in cells by selectively concentrating client proteins while excluding others. These functions are likely to be sensitive to the spatial organization of the scaffold proteins forming the condensate. We use coarse-grained molecular simulations to show that model intrinsically-disordered proteins phase separate into a heterogeneous, structured fluid characterized by a well-defined length scale. The proteins are modelled as semi-flexible polymers with punctate, multifunctional binding sites in good solvent conditions. Their dense phase is highly solvated with a spatial structure that is more sensitive to the separation of the binding sites than their affinity. We introduce graph theoretic measures to quantify their heterogeneity, and find that it increases with increasing binding site number, and exhibits multi-timescale dynamics. The model proteins also swell on passing from the dilute solution to the dense phase. The simulations predict that the structure of the dense phase is modulated by the location and affinity of binding sites distant from the termini of the proteins, while sites near the termini more strongly affect its phase behaviour. The relations uncovered between the arrangement of weak interaction sites on disordered proteins and the material properties of their dense phase can be experimentally tested to give insight into the biophysical properties, pathological effects, and rational design of biomolecular condensates. Model biomolecular condensates have heterogeneous material properties that are tuned by the number and distribution of their constituent proteins' sticky binding sites.