Model shows the role of intrinsically disordered proteins in biomolecular condensate viscoelasticity

Biomolecular condensates are membraneless organelles that organize biomolecules and aid in compartmentalizing cellular functions. Increasing evidence suggests that the material properties of these condensates, such as their viscoelastic response, are tightly linked to condensate function and dysfunction. However, the microscopic mechanisms by which protein sequences govern condensate material properties remain poorly understood.

Pablo Garcia and Jerelle Joseph demonstrated how the sequences of intrinsically disordered proteins (IDPs) control condensate viscoelasticity. Using coarse-grained molecular dynamics simulations, the authors modeled IDPs and analyzed their collective behavior to extract thermodynamic and time-dependent properties. They further resolve condensate microstructures by introducing approaches to quantify how heterogenous condensate meshes form and reconfigure at different timescales.

A central contribution of the study is the identification of design rules linking condensate microstructure to mechanical response.

“We show that having many different possible internal arrangements helps condensates behave more like elastic materials. We also emphasize that how well the components are connected matters: Networks with many overlapping, load-sharing connections are better at storing mechanical energy,” said Garcia.

The authors identified a microscopic mechanism for elastic force transmission that involves restoring elastic forces permeating throughout protein associative networks and depends on the relative timescales of meshwork reconfiguration and single-molecule shape memory. In addition, they developed a quantitative metric of this mechanism they call the condensate Deborah number, which correlates directly with viscoelastic behavior.

When examining dissipation mechanisms, the group found that decreasing IDP hydrophobicity reduces mesh heterogeneity but increases elasticity due to reduced frictional dissipation from compact chains.

They next look to incorporate long-range hydrodynamic interactions to include solvent-mediated correlations, improving the predictions of condensate material properties.

Source: “Molecular origins of viscoelasticity in biomolecular condensates,” by Pablo L. Garcia and Jerelle A. Joseph, Journal of Chemical Physics (2026). The article can be accessed at https://doi.org/10.1063/5.0309619 .

This paper is part of the Festschrift in honor of Kurt Kremer Collection, learn more here .