Sequence-encoded Conformation Pathways in Viscoelastic Microphase Separation of Multiblock Copolymers

Zhe-Peng Zhu; Jia-Ping Lin; Liang-Shun Zhang

doi:10.1007/s10118-026-3705-7

Your Location：

Home >

Browse articles >

Sequence-encoded Conformation Pathways in Viscoelastic Microphase Separation of Multiblock Copolymers

RESEARCH ARTICLE | Updated：2026-08-31

- Sequence-encoded Conformation Pathways in Viscoelastic Microphase Separation of Multiblock Copolymers
- Chinese Journal of Polymer Science Vol. 44, Issue 9, Pages: 3176-3188(2026)
- Affiliations：
  
  Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China
- Author bio：
  
  zhangls@ecust.edu.cn
- Funds：
- DOI：10.1007/s10118-026-3705-7
  CLC：
- Received：11 March 2026，
  
  Accepted：07 April 2026，
  
  Online First：01 July 2026，
  
  Published：05 September 2026
- Accepted：
Scan QR Code
Zhu, Z. P.; Lin, J. P.; Zhang, L. S. Sequence-encoded conformation pathways in viscoelastic microphase separation of multiblock copolymers. Chinese J. Polym. Sci. 2026, 44, 3176–3188

Zhe-Peng Zhu, Jia-Ping Lin, Liang-Shun Zhang. Sequence-encoded Conformation Pathways in Viscoelastic Microphase Separation of Multiblock Copolymers[J]. Chinese Journal of Polymer Science, 2026, 44(9): 3176-3188.
Zhu, Z. P.; Lin, J. P.; Zhang, L. S. Sequence-encoded conformation pathways in viscoelastic microphase separation of multiblock copolymers. Chinese J. Polym. Sci. 2026, 44, 3176–3188 DOI： 10.1007/s10118-026-3705-7.

Zhe-Peng Zhu, Jia-Ping Lin, Liang-Shun Zhang. Sequence-encoded Conformation Pathways in Viscoelastic Microphase Separation of Multiblock Copolymers[J]. Chinese Journal of Polymer Science, 2026, 44(9): 3176-3188. DOI： 10.1007/s10118-026-3705-7.

摘要

The sequence-encoded viscoelastic kinetics is introduced to direct non-equilibrium self-assembly pathways of multiblock copolymers and program their distinct conformation evolution

a capability that moves beyond the conventional design of static equilibrium nanostructures.

Abstract

Deciphering how molecular sequences of block copolymers program their self-assembly pathways is a pivotal pursuit in polymer science. To this end

we integrated viscoelastic constitutive relations into dynamic self-consistent field theory (DSCFT) to probe the spatiotemporally coupled evolution of nanostructures and chain conformations in sequence-defined multiblock copolymers during viscoelastic microphase separation. The DSCFT simulations reveal that the linear sequence of slow-relaxing “hard” and fast-relaxing “soft” blocks encodes two programmable kinetic motifs: a hard-soft-hard sequence drives a sharp

droplet-coalescence-triggered conversion from loop to bridge conformations during viscoelasticity-mediated phase inversion

whereas a soft-hard-soft sequence governs a gradual

network-contraction-driven relaxation of chain conformations. Serving as modular kinetic codes identified in the system of triblock copolymers

these kinetic motifs were shown to operate concurrently within tetrablock chains and generalize to penta- and hexa-block architectures

demonstrating the scalability and robustness of sequence-encoded dynamics. This work establishes the paradigm of sequence-encoded viscoelastic kinetics

providing a mechanism for controlling pathway-dependent self-assembly at the molecular level.

关键词

Keywords

references

Brangwynne, C. P.; Eckmann, C. R.; Courson, D. S.; Rybarska, A.; Hoege, C.; Gharakhani, J.; Jülicher, F.; Hyman, A. A. Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 2009 , 324 , 1729−1732..

Hyman, A. A.; Weber, C. A.; Jülicher, F. Liquid-liquid phase separation in biology. Annu. Rev. Cell Dev. Biol. 2014 , 30 , 39−58..

Shin, Y.; Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 2017 , 357 , eaaf4382..

Zwicker, D.; Paulin, O. W.; ter Burg, C. Physics of droplet regulation in biological cells. Rep. Prog. Phys. 2025 , 88 , 116601..

Alberti, S.; Gladfelter, A.;Mittag, T. Considerations and challenges in studying liquid -liquid phase separation and biomolecular condensates. Cell 2019 , 176 , 419−434..

Dignon, G. L.; Best, R. B.; Mittal, J. Biomolecular phase separation: from molecular driving forces to macroscopic properties. Annu. Rev. Phys. Chem. 2020 , 71 , 53−75..

Gomes, E.; Shorter, J. The molecular language of membraneless organelles. J. Biol. Chem. 2018 , 294 , 7115−7127..

[Li, P.; Banjade, S.; Cheng, H. C.; Kim, S.; Chen, B.; Guo, L.; Llaguno, M.; Hollingsworth, J. V.; King, D. S.; Banani, S. F.; Russo, P. S.; Jiang, Q. -X; Nixon, B. T.; Rosen, M. K. hase transitions in the assembly of multivalent signalling proteins. Nature 2012 , 483 , 336−340..

Pappu, R.V.; Cohen, S. R.; Dar, F.; Farag, M.; Kar, M. Phase transitions of associative biomacromolecules. Chem. Rev. 2023 , 123 , 8945−8987..

Wang, J.; Choi, J.-M.; Holehouse, A. S.; Lee, H.; Zhang, X.; Jahnel, M.; Maharana, S.; Lemaitre, R.; Pozniakovsky, A.; Drechsel, D.; Poser, I.; Pappu, R. V.; Albert i, S.; Hyman, A. A molecular grammar governing the driving forces for phase separation of prion-like rna binding proteins. Cell 2018 , 174 , 688−699..

Lin, Y.; Protter, D. S. W.; Rosen, M. K.; Parker, R. Formation and maturation of phase-separated liquid droplets by rna-binding proteins. Mol. Cell 2015 , 60 , 208−219..

Hnisz, D.; Shrinivas, K.; Young, R. A.; Chakraborty, A. K.; Sharp, P. A. Phase separation model for transcriptional control. Cell 2017 , 169 , 13−23..

Yamazaki, T.; Yamamoto, T.; Yoshino, H.; Souquere, S.; Nakagawa, S.; Pierron, G.; Hirose, T. Paraspeckles are constructed as block copolymer micelles. EMBO J. 2021 , 40 , e107270..

Choi, J.-M.; Holehouse, A. S.; Pappu, R. V. Physical principles underlying the complex biology of intracellular phase transitions. Annu. Rev. Biophys. 2020 , 49 , 107−133..

Alshareedah, I.; Moosa, M. M.; Banerjee, P. R. Programmable viscoelasticity in protein-rna condensates with disordered sticker-spacer polypeptides. Nat. Commun. 2021 , 12 , 6620..

Jawerth, L.; Fischer-Friedrich, E.; Saha, S.; Wang, J.; Franzmann, T.; Zhang, X.; Sachweh, J.; Ruer, M.; Ijavi, M.; Saha, S.; Mahamid, J.; Hyman, A. A.; Jülicher, F. Protein condensates as aging maxwell fluids. Science 2020 , 370 , 1317−1323..

Brady, J. P.; Farber, P. J.; Sekhar, A.; Lin, Y.-H.; Huang, R.; Bah, A.; Nott, T. J.; Chan, H. S.; Baldwin, A. J.; Forman-Kay, J. D.; Kay, L. E. Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation. Proc. Natl. Acad. Sci. U. S. A. 2017 , 114 , E8194−E8203..

Espinosa, J. R.; Joseph, J. A.; Sanchez-Burgos, I.; Garaizar, A.; Frenkel, D.; Collepardo-Guevara, R. Liquid network connectivity regulates the stability and composition of biomolecular condensates with many components. Proc. Natl. Acad. Sci. U. S. A. 2020 , 117 , 13238−13247..

Mittag, T.; Pappu, R. V. A conceptual framework for understanding phase separation and addressing open questions and challenges. Mol. Cell 2022 , 82 , 2201−2214..

Farag, M.; Cohen, S. R.; Borcherds, W. M.; Bremer, A.; Mittag, T.; Pappu, R. V. Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations. Nat. Commun. 2022 , 13 , 7722..

Dar, F.; Cohen, S. R.; Mitrea, D. M.; Phillips, A. H.; Nagy, G.; Leite, W. C.; Stanley, C. B.; Choi, J.-M.; Kriwacki, R. W.; Pappu, R. V. Biomolecular condensates form spatially inhomogeneous network fluids. Nat. Commun. 2024 , 15 , 3413..

Wu, T.; King, M. R.; Qiu, Y.; Farag, M.; Pappu, R. V.; Lew, M. D. Single-fluorogen imaging reveals distinct environmental and structural features of biomolecular condensates. Nat. Phys. 2025 , 21 , 778−786..

Tejedor, A. R.; Sanchez-Burgos, I.; Estevez-Espinosa, M.; Garaizar, A.; Collepardo-Guevara, R.; Ramirez, J.;Espinosa, J. R. Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but rna can prevent it. Nat. Commun. 2022 , 13 , 5717..

Lin, Y.; Forman-Kay, J. D.; Chan, H. S. Theories for sequence-dependent phase behaviors of biomolecular condensates. Biochemistry 2018 , 57 , 2499−2508..

Joseph, J. A.; Reinhardt, A.; Aguirre, A.; Chew, P. Y.; Russell, K. O.; Espinosa, J. R.; Garaizar, A.; Collepardo-Guevara, R. Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy. Nat. Comput. Sci. 2021 , 1 , 732−743..

Dignon, G. L.; Zheng, W.; Kim, Y. C.; Best, R. B.; Mittal, J. Sequence determinants of protein phase behavior from a coarse-grained model. PLoS Comput. Biol. 2018 , 14 , e1005941..

Bates, F. S.; Hillmyer, M. A.; Lodge, T. P.; Bates, C. M.; Delaney, K. T.; Fredrickson, G. H. Multiblock polymers: panacea or pandora’s box. Science 2012 , 336 , 434−440..

Lutz, J. F.; Ouchi, M.; Liu, D. R.; Sawamoto, M. Sequence-controlled polymers. Science 2013 , 341 , 1238149..

Li, J.; Stayshich, R. M.; Meyer, T. Y. Exploiting sequence to control the hydrolysis behavior of biodegradable plga copolymers. J. Am. Chem. Soc. 2011 , 133 , 6910−6913..

Matyjaszewski, K. Architecturally complex polymers with controlled heterogeneity. Science 2011 , 333 , 1104−1105..

Pinheiro, V. B.; Taylor, A. I.; Cozens, C.; Abramov, M.; Renders, M.; Zhang, S.; Chaput, J. C.; Wengel, J.; Peak-Chew, S.-Y.; McLaughlin, S. H.; Herdewijn, P.; Holliger, P. Synthetic genetic polymers capable of heredity and evolution. Science 2012 , 336 , 341−344..

Lewandowski, B.; De Bo, G.; Ward, J. W.; Papmeyer, M.; Kuschel, S.; Aldegunde, M. J.; Gramlich, P. M. E.; Heckmann, D.; Goldup, S. M.; D’Souza, D. M.; Fernandes, A. E.; Leigh, D. A. Sequence-specific peptide synthesis by an artificial small-molecule machine. Science 2013 , 339 , 189−193..

Xu, Z.; Dong, Q.; Li, W. Architectural design of block copolymers. Macromolecules 2024 , 57 , 1869−1884..

Ran, X.; Dong, Q.; Peng, L.; Huang, X.; Li, W. Program asymmetric binary packing lattices of ab1cb2 tetrablock terpolymers. Macromolecules 2025 , 58 , 9851−9861..

Chen, T.; Xu, Z.; Chu, X.; Peng, L.; Huang, X.; Li, W. A simulation study on the effect of tailoring molecular architectures on the mechanical behaviors of lamella-forming BABCB linear multiblock copolymers. Macromolecules 2025 , 58 , 6387−6398..

Chu, X.; Xu, Z.; Cao, Y.; Li, W. Simulation study on the mechanical properties of lamella-forming ABABA linear multiblock copolymers. Macromolecules 2024 , 57 , 9536−9545..

Schmid, F. Understanding and modeling polymers: the challenge of multiple scales. ACS Polym. Au 2023 , 3 , 28−49..

Schmid, F.; Li, B. Dynamic self-consistent field approach for studying kinetic processes in multiblock copolymer melts. Polymers 2020 , 52 , 2205..

Park, S. J.; Myers, T.; Liao, V.; Jayaraman, A. Self-consistent field theory and coarse-grained molecular dynamics simulations of pentablock copolymer melt phase behavior. Mol. Syst. Des. Eng. 2024 , 9 , 1235−1253..

Lequieu, J.; Quah, T.; Delaney, K. T.; Fredrickson, G. H. Complete photonic band gaps with nonfrustrated ABC bottlebrush block polymers. ACS Macro Lett. 2020 , 9 , 1074−1080..

Arora, A.; Qin, J.; Morse, D. C.; Delaney, K. T.; Fredrickson, G. H.; Bates, F. S.; Dorfman, K. D. Broadly accessible self-consistent field theory for block polymer materials discovery. Macromolecules 2016 , 49 , 4675−4690..

Tsai, C. C; Fredrickson, G. H. Using particle swarm optimization and self-consistent field theory to discover globally stable morphologies of block copolymers. Macromolecules 2022 , 55 , 5249−5262..

Tyler, C. A.; Qin, J.; Bates, F. S.; Morse, D. C. SCFT study of nonfrustrated ABC triblock copolymer melts. Macromolecules 2007 , 40 , 4654−4668..

Lequieu, J.; Koeper, T.; Delaney, K. T.; Fredrickson, G. H. Extreme deflection of phase boundaries and chain bridging in A(BA′)n miktoarm star polymers. Macromolecules 2020 , 53 , 513−522..

Subbotin, A.; Klymko, T.; ten Brinke, G. Lamellar-in-lamellar structure of A-B-(B-B-C) m -B-B-A multiblock copolymers. Macromolecules 2007 , 40 , 2915−2918..

Miglani, C.; Ralhan, J.; Banoo, M.; Nath, D.; Sil, S.; Pal, S. K.; Gautam, U. K.; Pal, A. Stimuli-responsive control over self-assembled nanostructures in sequence-specific functional block copolymers. ACS Polym. Au 2024 , 4 , 255−265..

MacEwan, S. R.; Weitzhandler, I.; Hoffmann, I.; Genzer, J.; Gradzielski, M.; Chilkoti, A. Phase behavior and self-assembly of perfectly sequence-defined and monodisperse multiblock copolypeptides. Biomacromolecules 2017 , 18 , 599−609.

Roberts, S.; Harmon, T. S.; Schaal, J. L.; Miao, V.; Li, K.; Hunt, A.; Wen, Y.; Oas, T. G.; Collier, J. H.; Pappu R. V.; Chilkoti, A. Injectable tissue integrating networks fromrecombinant polypeptides with tunable order. Nat. Mater. 2018 , 17 , 1154−1163..

Dzuricky, M.; Rogers, B. A.; Shahid, A.; Cremer, P. S.; Chilkoti, A. De novo engineering of intracellular condensates using artificial disordered proteins. Nat. Chem. 2020 , 12 , 814−825..

Choi, J.-W.; Choi, S.-H.; Won, J.-I. Self-assembly behavior of elastin-like polypeptide diblock copolymers containing a charged moiety. Biomacromolecules 2021 , 22 , 2604−2613..

Patterson, A. L.; Danielsen, S. P. O.; Yu, B.; Davidson, E. C.; Fredrickson, G. H.; Segalman, R. A. Sequence effects on block copolymer self assembly through tuning chain conformation and segregation strength utilizing sequence defined polypeptoids. Macromolecules 2019 , 52 , 1277−1286..

Khandpur, A. K.; Förster, S.; Bates, F. S.; Hamley, I. W.; Ryan, A. J.; Bras, W.; Almdal, K.; Mortensen, K. Polyisoprene polystyrene diblock copolymer phase diagram near the order-disorder transition. Macromolecules 1995 , 28 , 8796−8806..

Colby, R. H. Block copolymer dynamics. Curr. Opin. Colloid Interface Sci. 1996 , 1 , 454−465..

Wu, L.; Cochran, E. W.; Lodge, T. P.; Bates, F. S. Consequences of block number on the order-disorder transition and viscoelastic properties of linear (AB)n multiblock copolymers. Macromolecules 2004 , 37 , 3360−3368..

Kim, T.; White, J. M.; Bates, F. S.; Lodge, T. P. Universal viscoelastic response of body centered cubic block copolymer solutions: time-temperature-concentration superposition. Macromolecules 2025 , 58 , 5579−5589..

Lenoch, A.; Schönhoff, M.; Cramer, C. Relaxing, fast and slow: linear viscoelasticity and dynamics in mixed cross-linker metallosupramolecular networks. Macromolecules 2024 , 57 , 11507−11519..

Tanaka, H.; Araki, T. Phase inversion during viscoelastic phase separation: roles of bulk and shear relaxation moduli. Phys. Rev. Lett. 1997 , 78 , 4966−4969..

Tanaka, H. Viscoelastic phase separation in biological cells. Commun. Phys. 2022 , 5 , 167..

Fernández-Rico, C.; Schreiber, S.; Oudich, H.; Lorenz, C.; Sicher, A.; Sai, T.; Bauernfeind, V.; Heyden, S.; Carrara, P.; De Lorenzis, L.; Style, R. W.; Dufresne, E. R. Elastic microphase separation produces robust bicontinuous materials. Nat. Mater. 2024 , 23 , 124−130..

Huo, Y.; Zhang, H.; Yang, Y. The morphology and dynamics of the viscoelastic microphase separation of diblock copolymers. Macromolecules 2003 , 36 , 5383−5391..

Yoshimoto, K.; Taniguchi, T. Viscoelastic phase separation model for ternary polymer solutions. J. Chem. Phys. 2021 , 154 , 104903..

Tanaka, H. Formation of network and cellular structures by viscoelastic phase separation. Adv. Mater. 2009 , 21 , 1872−1880..

Tanaka, H.; Nishikawa, Y. Viscoelastic phase separation of protein solutions. Phys. Rev. Lett. 2005 , 95 , 078103..

Shi, W.; Yang, J.; Liu, W.; Zhang, L.; Han C. C. Anomalous phase separation dynamics under asymmetric viscoelastic effect: where fluidic and elastic properties meet. Macromolecules 2013 , 46 , 2516−2520..

Shi, W.; Chen, F.; Zhang, Y.; Han, C. C. Viscoelastic phase separation and interface assisted crystallization in a highly immiscible ipp/pmma blend. ACS Macro Lett. 2012 , 1 , 1086−1089..

Tsai, C.-C.; Xu, J.; Duclos, C.; Xie, S. Microstructure and viscoelasticity of oppositely charged ionomer blend melts. Macromolecules 2025 , 58 , 1608−1620..

Rapp, P. B.; Silverman, B. R. Viscoelastic phase patterning in artificial protein hydrogels. Macromolecules 2022 , 55 , 3201−3207..

Surendran, A.; Joy, J.; Parameswaranpillai, J.; Anas, S.; Thomas, S. An overview of viscoelastic phase separation in epoxy based blends. Soft Matter 2020 , 16 , 3363−3377..

Jose, J.; Joseph, K.; Pionteck, J.; Thomas, S. Pvt behavior of thermoplastic poly(styrene-co-acrylonitrile)-modified epoxy systems: relating polymerization-induced viscoelastic phase separation with the cure shrinkage performance. J. Phys. Chem. B 2008 , 112 , 14793−14803..

Zhu, Z.; Lin, J.; Zhang, L. Breaking composition constraints: viscoelasticity-driven phase inversion for mechanically robust block copolymer networks. Macromolecules 2026 , 59 , 312−325..

Müller, M.; Schmid, F. Incorporating fluctuations and dynamics in self-consistent field theories for polymer blends. Adv. Polym. Sci. 2005 , 185 , 1−58..

Fraaije, J. G. E. M.; Vlimmeren, B. A. C.; Maurits, N. M.; Postma, M.; Evers, O. A.; Hoffmann, C.; Altevogt, P.; Goldbeck–Wood, G. The dynamic mean-field density functional method and its application to the mesoscopic dynamics of quenched block copolymer melts. J. Chem. Phys. 1997 , 106 , 4260−4269..

Zhang, L.; Sevink, A.; Schmid, F. Hybrid lattice boltzmann/dynamic self-consistent field simulations of microphase separation and vesicle formation in block copolymer systems. Macromolecules 2011 , 44 , 9434−9447..

[Doi, M.; Onuki, A. Dynamic coupling between stress and composition in polymer solutions and blends. J. Phys. II France 1992 , 2 , 1631-1656..

Hall, D. M.; Lookman, T.; Fredrickson, G. H.; Banerjee, S. Hydrodynamic self-consistent field theory for inhomogeneous polymer melts. Phys. Rev. Lett. 2006 , 97 , 114501..

[Fredrickson, G. H. The equilibrium theory of inhomogeneous polymers ; Oxford University Press: New York, 2013 ..

[Tanaka, H. Viscoelastic model of phase separation. Phys. Rev. E 1997, 56 , 4451–4462..

Hall, D. M.; Lookman, T.; Fredrickson, G. H.; Banerjee, S. Numerical method for hydrodynamic transport of inhomogeneous polymer melts. J. Comput. Phys. 2007 , 224 , 681−698..

Matsen, M. W.; Thompson, R. B. Equilibrium behavior of symmetric aba triblock copolymer melts. J. Chem. Phys. 1999 , 111 , 7139−7146..

Drolet, F.; Fredrickson, G. H. Optimizing chain bridging in complex block copolymers. Macromolecules 2001 , 34 , 5317−5324..

Zhang, L.; Lin, J.; Lin, S. Morphologies and bridging properties of graft copolymers. J. Phys. Chem. B 2007 , 111 , 351−357..

Araki, T.; Tanaka, H. Three-dimensional numerical simulations of viscoelastic phase separation: morphological characteristics. Macromolecules 2001 , 34 , 1953−1963..

White, J. M.; Kim, T.; Bates, F. S.; Lodge, T. P. How does the rate of chain exchange relate to stress relaxation in triblock copolymer networks. ACS Cent. Sci. 2025 , 11 , 422−430..

Kim, T.; White, J. M.; Magruder, B. R.; Danielson, E.; Bates, F. S.; Lodge, T. P. Concentration-driven slowdown of chain-exchange kinetics in block copolymer micelle solutions. Macromolecules 2025 , 58 , 10580−10590..

Prhashanna, A.; Dormidontova, E. E. Micelle self-assembly and chain exchange kinetics of tadpole block copolymers with a cyclic corona block. Macromolecules 2020 , 53 , 982−991..

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Synthesis and Properties of Poly(ethylene succinate)-b-poly(butylene carbonate) Multiblock Copolymers

Optimization of Linear Sequence-controlled Copolymers for Maximizing Adsorption Capacity

End-group and Side-chain Dual-engineering of Selenium-fused Acceptors for 20.08% Efficiency Polymer Solar Cells with Low Energy Loss

Advances in Polymer-based Circularly Polarized Luminescent Materials

Upgrading Commercially Available Polyethylene to High-value Materials with Strong Mechanical Performance and Hydrophilicity by Blending with Ethylene/meta-Methoxystyrene Copolymers

Related Author

Zi-Qing Wang

Xu-Cheng Du

Zhen-Chao Li

Ai-Min Mao

Pei-Xian Wang

Jun Ma

Qiu-Ju Chen

Xing-Hua Zhang

Related Institution

School of Chemistry and Chemical Engineering/State Key Laboratory Incubation Base for Green Processing of Chemical Engineering, Shihezi University

Xinjiang Blue Ridge Tunhe Polyester Co., Ltd.

School of Physical Sciences and Engineering, Beijing Jiaotong University

Beijing Key Laboratory of Novel Materials Genetic Engineering and Application for Rail Transit, Beijing Jiaotong University

School of Physics and Astronomy, Beijing Normal University

⁰