The mechanobiology of biomolecular condensates

The central goal of mechanobiology is to understand how the mechanical forces and material properties of organelles, cells, and tissues influence biological processes and functions. Since the first description of biomolecular condensates, it was hypothesized that they obtain material properties that are tuned to their functions inside cells. Thus, they represent an intriguing playground for mechanobiology. The idea that biomolecular condensates exhibit diverse and adaptive material properties highlights the need to understand how different material states respond to external forces and whether these responses are linked to their physiological roles within the cell. For example, liquids buffer and dissipate, while solids store and transmit mechanical stress, and the relaxation time of a viscoelastic material can act as a mechanical frequency filter. Hence, a liquid-solid transition of a condensate in the force transmission pathway can determine how mechanical signals are transduced within and in-between cells, affecting differentiation, neuronal network dynamics, and behavior to external stimuli. Here, we first review our current understanding of the molecular drivers and how rigidity phase transitions are set forth in the complex cellular environment. We will then summarize the technical advancements that were necessary to obtain insights into the rich and fascinating mechanobiology of condensates, and finally, we will highlight recent examples of physiological liquid-solid transitions and their connection to specific cellular functions. Our goal is to provide a comprehensive summary of the field on how cells harness and regulate condensate mechanics to achieve specific functions.