Sequence-dependent self-coacervation in high charge-density polyampholytes

Abstract

Experiment and theory show how charge monomer sequence can be used to control self-coacervation in blocky polyampholytes.

Recent progress in the science of complex coacervation

“…For instance, synthetic polypeptides have been used extensively as a model polymer system where different side chain functionalities can be introduced along the same backbone. 35,[43][44][45]55,75,77,136 Additionally, solid-phase synthesis enables precise control over chemical sequence, 70,[137][138][139][140][141][142][143] and can be combined with methods for controlled polymerization to allow for the preparation of well-controlled comb polymer architectures. 46,144 Controlled polymerization also has allowed for the synthesis of random copolymers to facilitate the introduction of multiple functionalities.…”

“…The same team demonstrated qualitative matching was also observed for self-coacervation of a variety of sequence-defined polyampholytes, once again using polypeptides (Figure 15c,d). 138 Alternative theoretical approaches have also been considered to understand the role of polyelectrolyte sequence in coacervation, especially for sequence-defined polyampholytes due to their close connection to biophysical IDP systems. Danielsen and coworkers used the field theoretic framework, 104 in close connection with MD simulations, to understand the role of sequences of polyampholyte self-coacervation.…”

“…105,106 This work focuses on the fluctuation-induced attraction between sequenced polyampholytes, but the general sequence trends are consistent with later work on high charge-density systems, such as the aforementioned transfer matrix theory from Sing and Perry (Figure 15c,d) that compares favorably with experiment. 138…”

“…Liq., 228, Lin et al, Random-phase-approximation theory for sequence-dependent, biologically functional liquid-liquid phase separation of intrinsically disordered proteins, 176-193, Copyright 2017, with permission from Elsevier. (c) Polyampholyte phase diagrams from Madinya et al calculated via the sequence-defined transfer matrix theory, also showing an increase in the two-phase region with increasing block length (τ/2) 138. (d) Salt resistance c rS and critical salt concentration c cr s in (c) as a function of τ for both polyampholytes (red) and homopolyelectrolytes (blue), compared with experimental measurements (inset) of the same quantity from sequence-defined polypeptides 138.…”

100th Anniversary of Macromolecular Science Viewpoint: Opportunities in the Physics of Sequence-Defined Polymers

“…The authors have used particle-based simulations to study complex coacervation for a wide range of polyelectrolyte sequences, 84,85 which also inform theories that specifically consider how local correlations arising from charge packing and charged-monomer sequence govern phase behavior (Figure 3b,c). 84,88,99,100 Our view is that the theoretical and computational study of sequence-defined polymers must take advantage of the full suite of computational and theoretical tools, connecting the monomer-level resolution inherent to particle-based methods to larger length-scale methods, such as field theory, that can be used to determine polymer morphology and structure. In a similar spirit, integration of theory/simulation, characterization, and synthesis is crucial to (i) interpret experimental results based on ensemble averaged quantities and (ii) refine the approximations that must be made to account for disparate length/sequence scales.…”