Hugo Le Roy
EPFL, Switzerland
Entropic Clustering of Stickers Induces Aging in Biocondensates
Biomolecular condensates are membrane-less comparments in the cell that are involved in a wide diversity of biological processes. These liquid-liquid phase-separated droplets exhibit a viscoelastic mechanical response. A behavior that is rationalized by modeling the complex molecules that make up a condensate as stickers and spacers which can assemble into a network-like structure. The proper functioning of biocondensates requires precise control over their composition, size, and mechanical response. For example, several neurodegenerative diseases are associated with dysfunctional condensates that solidify over a long period of time (days) until they become solid. A phenomenon usually described as aging. The emergence of such a long timescale of evolution from microscopic events, as well as the structural reorganization that leads to aging remains mostly an open question. To explore the connection between the mechanical properties of the condensates and their structure, we use a simplified description of the condensates. In our framework, a condensate is considered as an associative gel made of polymers (RNA) and linkers (DEAD-box proteins), whose response time is related to the interaction time between the constituents. We show that the interaction between linkers and long polymers results in an attractive Casimir force between linkers. As a consequence, linkers tend to cluster over equilibration of the network. Such a clustering does not make the material stiffer but leads to an exponential increase of the relaxation timescale in agreement with experimental observations.
