A rigidity phase transition of Stomatin condensates governs a switch from transport to mechanotransduction

Abstract

A large body of work suggests that biomolecular condensates ensuing from liquid-liquid phase separation mature into various material states. How this aging process is controlled and if the naive and mature phases can have differential functions is currently unknown. Using Caenorhabditis elegans as a model, we show that MEC-2 Stomatin undergoes a rigidity phase transition during maturation from fluid to viscoelastic, glass-like condensates that facilitate either transport or mechanotransduction. This switch is promoted by the SH3 domain of UNC-89/Titin/Obscurin through a direct interaction with MEC-2 and suggests a physiological role for a percolation transition in force transmission during body wall touch. Together, our data demonstrate a novel function for rigidity maturation during mechanotransduction and a previously unidentified role for Titin homologs in neurons.

Time-shared optical tweezers for active microrheology inside cells

“…In the last decades, optical trapping has become an exquisite tool for characterizing the mechanical properties of biological samples. [1][2][3] Some of the multimodal applications offered by this technology are DNA stretching, 4 biomolecular condensate viscoelastic maturation, 5,6 cell membrane tension propagation 7 or cell nucleus stiffness measurements. 8 Among those, intracellular microrheology in vivo 9,10 and in vitro 11,12 aim at the material viscoelasticity of different cellular compartments, such as the cytoplasm.…”

Linking modulation of bio-molecular phase behaviour with collective interactions

“…Many examples have been found where the formation of these liquid-like, proteinand/or RNA-rich droplets serves physiological functions in cells [2][3][4][5] or is implicated in neurodegenerative diseases [6,7]. Furthermore, the liquid nature of the droplets leads to dynamic processes such as ripening [1,[8][9][10][11], wetting [12,13] and ageing [14][15][16][17], which can participate in or interfere with normal biological processes [7,18,19]. There is thus a huge interest in understanding the driving forces of bio-molecular condensate formation and mechanisms of action of modulators.…”