Membraneless compartments based on intrinsically disordered proteins: from biology towards new protein materials
Paolo Arosio, Institute for Chemical and Bioengineering, ETH Zurich
In the last few years, discoveries in biology are revealing that a class of intrinsically disordered protein sequences plays an important role in the formation of cellular membraneless compartments by spontaneous liquid-liquid phase separation of proteins and nucleic acids. These compartments underlie several important functions and can act as microreactors, in which environment and composition are carefully regulated in space and time. These observations inspired us to exploit these biological sequences to mimic these membraneless compartments on the bench, towards the development of high-performance open microreactors, with applications for instance in biocatalysis. With these sequences we can regulate not only the dynamic process of phase separation but also several properties of the resulting compartments, including uptake of client molecules, polarity and material properties. With this control we can, in turn, regulate biochemical reactions occurring within the compartments.
We further show the development of droplet microfluidic platforms to characterize multiple properties of the open compartments, including both thermodynamics and dynamics of phase separation. We illustrate these concepts by investigating an established in vitro model of Processing bodies consisting of the phase separation of the DEAD-box protein ATPase Dhh1 in the presence of ATP and RNA.
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