Sequence and entropy-based control of complex coacervates

Abstract

Biomacromolecules rely on the precise placement of monomers to encode information for structure, function, and physiology. Efforts to emulate this complexity via the synthetic control of chemical sequence in polymers are finding success; however, there is little understanding of how to translate monomer sequence to physical material properties. Here we establish design rules for implementing this sequence-control in materials known as complex coacervates. These materials are formed by the associative phase separation of oppositely charged polyelectrolytes into polyelectrolyte dense (coacervate) and polyelectrolyte dilute (supernatant) phases. We demonstrate that patterns of charges can profoundly affect the charge–charge associations that drive this process. Furthermore, we establish the physical origin of this pattern-dependent interaction: there is a nuanced combination of structural changes in the dense coacervate phase and a 1D confinement of counterions due to patterns along polymers in the supernatant phase.

Evolved sequence features within the intrinsically disordered tail influence FtsZ assembly and bacterial cell division

“…Similar results were observed by altering the patterning of oppositely charged residues within the IDR of DDX4, a protein that forms nuage bodies (Nott et al, 2015). Theories show that the driving forces for phase separation become stronger and the salt dependence becomes weaker with increased separation of charged residues (Chang et al, 2017;Lin et al, 2016Lin et al, , 2018. Taken together our results suggest that the lack of CTL sequences above and below the thresholds shown in Figure 1C derives from a combination of considerations including maintaining FtsZ concentrations within the cell and minimizing tail-totail associations that lead to strong albeit aberrant multivalent interactions amongst segregated blocks of charge within CTTs.…”

Dynamic Synthetic Cells Based on Liquid–Liquid Phase Separation

“…A) Schematic representation of segregativea nd associative LLPS. Recent studies in this area have soughtt ou nderstand these factors in greaterd etail by using computational modelling combined with better-defined polyelectrolyte structures, [25] in terms of, for example, polymerl ength dispersity, [26] charge distribution, [27] chirality [28] or base pairing. The ATPS is made of PEG and dextran doped with fluorescein-isothiocyanate (FITC)-labelled PEG (cyan) and rhodamine-isothiocyanate (RITC)-tagged dextran (magenta); the complex coacervate droplets are assembled from polyethyleneimine (PEI) and DNA doped with FITC-tagged DNA and RITC-labelled PEI.C)Schematic phase diagram for ATPS systems, showing phase separation above thresholdconcentrationsofp olymers.…”

Phase separation: Bridging polymer physics and biology

“…Fortunately, a combination of experimental efforts using model systems, as well as the development of new analytical techniques, is helping to address this issue. For instance, a combination of experimental and computational approaches were recently used to highlight the importance of entropic effects in driving the complex coacervation of polypeptides with different patterns of charge [122]. In particular, this insight into the entropic nature of complex coacervation highlights the importance of sequence effects, rather than overall composition, and provides intuition regarding the design of such systems.…”