Membraneless organelles like stress granules are active liquid-liquid phase-separated droplets that are involved in many intracellular processes. Their active and dynamic behavior is often regulated by ATP-dependent reactions. However, how exactly membraneless organelles control their dynamic composition remains poorly understood. Herein, we present a model for membraneless organelles based on RNA-containing active coacervate droplets regulated by a fuel-driven reaction cycle. These droplets emerge when fuel is present, but decay without. Moreover, we find these droplets can transiently up-concentrate functional RNA which remains in its active folded state inside the droplets. Finally, we show that in their pathway towards decay, these droplets break apart in multiple droplet fragments. Emergence, decay, rapid exchange of building blocks, and functionality are all hallmarks of membrane-less organelles, and we believe that our work could be powerful as a model to study such organelles.
In biology, self-assembly of proteins
and energy-consuming reaction
cycles are intricately coupled. For example, tubulin is activated
and deactivated for assembly by a guanosine triphosphate (GTP)-driven
reaction cycle, and the emerging microtubules catalyze this reaction
cycle by changing the microenvironment of the activated tubulin. Recently,
synthetic analogs of chemically fueled assemblies have emerged, but
examples in which assembly and reaction cycles are reciprocally coupled
remain rare. In this work, we report a peptide that can be activated
and deactivated for self-assembly. The emerging assemblies change
the microenvironment of their building blocks, which consequently
accelerate the rates of building block deactivation and reactivation.
We quantitatively understand the mechanisms at play, and we are thus
able to tune the catalysis by molecular design of the peptide precursor.
The front cover artwork is provided by BoekhovenLab at TU Munich. The image shows an energy landscape of kinetically trapped chemically fueled supramolecular fibers, which reminds of a mountain landscape. Read the full text of the Research Article at 10.1002/syst.202200035.
Nature uses dynamic, molecular self‐assembly to create cellular architectures that adapt to their environment. For example, a guanosine triphosphate (GTP)‐driven reaction cycle activates and deactivates tubulin for dynamic assembly into microtubules. Inspired by dynamic self‐assembly in biology, recent studies have developed synthetic analogs of assemblies regulated by chemically fueled reaction cycles. A challenge in these studies is to control the interplay between rapid disassembly and kinetic trapping of building blocks known as dynamic instabilities. In this work, we show how molecular design can tune the tendency of molecules to remain trapped in their assembly. We show how that design can alter the dynamic of emerging assemblies. Our work should give design rules for approaching dynamic instabilities in chemically fueled assemblies to create new adaptive nanotechnologies.
About ten years ago, chemically fueled systems have emerged as a new class of synthetic materials with tunable properties. Yet, applications of these materials are still scarce. In part, this is due to an incomplete characterization of the viscoelastic properties of those materials, which has – so far – mostly been limited to assessing their linear response under shear load. Here, we fill some of these gaps by comparing the viscoelastic behavior of two different, carbodiimide fueled Fmoc-peptide systems. We find that both, the linear and non-linear response of the hydrogels formed by those Fmoc-peptides depends on the amount of fuel driving the self-assembly process – but hardly on the direction of force application. In addition, we identify the concentration of accumulated waste products as a novel, so far neglected parameter that crucially affects the behavior of such chemically fueled hydrogels. With the mechanistic insights gained here, it should be possible to engineer a new generation of dynamic hydrogels with finely tunable material properties that can be tailored precisely for such applications, where they are challenged by mechanical forces.
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