Origin of the Anomalous Guest Polymer Selectivity in Complex Coacervates.
4 affiliations
- 1Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong999077, China.
- 2Institute of Chemistry, University of Campinas (UNICAMP), P.O. Box 6154, 13083-970Campinas, São Paulo, Brazil.
- 3Department of Chemical and Biomolecular Engineering, University of Massachusetts Amherst, Amherst, Massachusetts01003, United States.
- 4Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California91125, United States.
Abstract
Complex coacervates─liquid condensates resulting from liquid-liquid phase separation of oppositely charged polymers─have attracted broad interest in artificial cells, drug delivery vehicles, and smart nanoreactors. The functionality of these applications is significantly influenced by the coacervate's ability to encapsulate guest macromolecules, where the guest interactions determine their loading efficiency and activity. Using MD simulations, analytical theory, and experiments, we demonstrate that the intrinsic electrostatic correlations within the coacervate matrix significantly modify the effective interactions of guest polymers in the dense phase, resulting in the strong dependence of encapsulation on guest chain length, charge density, and charge sequence observed experimentally. Even in the absence of chemical incompatibility, neutral polymers are strongly excluded from the coacervate phase as a result of disrupting electrostatic correlations within coacervates. Consequently, the encapsulation efficiency of neutral polymers exponentially decays with increasing guest chain length. For polyampholyte-like intrinsically disordered proteins (IDPs), their effective interaction within coacervates is largely determined by charge sequence: IDPs with more-disordered sequences experience strict rejection from the dense phase, whereas those with more blocky charges are dispersed within coacervates. Interestingly, for all the guest species tested, their effective interactions are opposite to those observed in dilute solutions, where the sign of the effective two-body interaction reverses when going from the dilute phase to the dense coacervate phase. We elucidate that the non-trivial guest selectivity in complex coacervates originates from the disruption of polycation-polyanion electrostatic correlations by the guest, which combines an energetic penalty (dilution of charge density) with an entropic penalty (loss of chain conformational freedom of the host). These findings have significant implications for understanding guest behavior in coacervate and biocondensate systems.
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BibTeX
@article{wu2026origin,
title = {{Origin of the Anomalous Guest Polymer Selectivity in Complex Coacervates.}},
author = {Zongpei Wu and Júlia Bonesso Sabadini and Pierre J Walker and Watson Loh and Zhen-Gang Wang and Sarah L Perry and Shensheng Chen},
journal = {ACS nano},
year = {2026},
month = oct,
doi = {10.1021/acsnano.6c06413},
url = {https://europepmc.org/article/MED/42917213},
note = {CC BY},
}
RIS
TY - JOUR
TI - Origin of the Anomalous Guest Polymer Selectivity in Complex Coacervates.
AU - Zongpei Wu
AU - Júlia Bonesso Sabadini
AU - Pierre J Walker
AU - Watson Loh
AU - Zhen-Gang Wang
AU - Sarah L Perry
AU - Shensheng Chen
PY - 2026
DA - 2026/10/01
JO - ACS nano
DO - 10.1021/acsnano.6c06413
UR - https://europepmc.org/article/MED/42917213
AB - Complex coacervates─liquid condensates resulting from liquid-liquid phase separation of oppositely charged polymers─have attracted broad interest in artificial cells, drug delivery vehicles, and smart nanoreactors. The functionality of these applications is significantly influenced by the coacervate's ability to encapsulate guest macromolecules, where the guest interactions determine their loading efficiency and activity. Using MD simulations, analytical theory, and experiments, we demonstrate that the intrinsic electrostatic correlations within the coacervate matrix significantly modify the effective interactions of guest polymers in the dense phase, resulting in the strong dependence of encapsulation on guest chain length, charge density, and charge sequence observed experimentally. Even in the absence of chemical incompatibility, neutral polymers are strongly excluded from the coacervate phase as a result of disrupting electrostatic correlations within coacervates. Consequently, the encapsulation efficiency of neutral polymers exponentially decays with increasing guest chain length. For polyampholyte-like intrinsically disordered proteins (IDPs), their effective interaction within coacervates is largely determined by charge sequence: IDPs with more-disordered sequences experience strict rejection from the dense phase, whereas those with more blocky charges are dispersed within coacervates. Interestingly, for all the guest species tested, their effective interactions are opposite to those observed in dilute solutions, where the sign of the effective two-body interaction reverses when going from the dilute phase to the dense coacervate phase. We elucidate that the non-trivial guest selectivity in complex coacervates originates from the disruption of polycation-polyanion electrostatic correlations by the guest, which combines an energetic penalty (dilution of charge density) with an entropic penalty (loss of chain conformational freedom of the host). These findings have significant implications for understanding guest behavior in coacervate and biocondensate systems.
SN - 1936-0851
SN - 1936-086X
ER -