Emergent mechanics of a networked multivalent protein condensate

Recent studies indicate that simple one- or two-component protein condensates behave as Maxwell fluids. As protein interactions become more complex with an increasing number of components, these condensates are expected to exhibit novel mechanical behaviors beyond those of Maxwell fluids. In this study [1], we measure the mechanical properties of a functional multivalent protein condensate reconstituted with six postsynaptic density proteins (6xPSD) using AFM-based mesoscale rheology, in conjunction with quantitative fluorescence characterization. The 6xPSD phase separates into condensate droplets via multivalent interactions and oligomerization upon mixing. A key finding of this investigation is that 80% of the 6xPSD proteins are mobile, diffusing in a dynamically crosslinked network formed by the remaining 20% non-mobile scaffold proteins. This unique structure produces a two-mode relaxation modulus, which decays exponentially at short times and then follows a power-law decay over long times. The power-law rheology, with an exponent close to 0.5, is a hallmark of the binding/unbinding dynamics of weak bonds in protein networks, allowing for rearrangements over long times. Our work provides a reliable platform for investigating the mechanics of multivalent protein condensates and their relationships to physiological functions and diseases.

[1] Liao, Z., Jia, B., Guan, D., Chen, X., Zhang, M., & Tong, P. Nature Communications, 16(1), 5237 (2025).