Macromolecular Fingerprints and Thermodynamic–Kinetic Regulation of Liquid–Liquid Phase Separation in Polysaccharide-Derived Biocondensates
- 1University of New Hampshire , , , ,
Abstract
The relationship between chemical functionalization and the thermoresponsive phase separation of polysaccharide-derived biocondensates remains insufficiently investigated. In this study, we systematically examine how the substitution site, polymer concentration, solvent environment, and thermal history influence the phase behavior of methacrylated dextran derivatives using multidimensional nuclear magnetic resonance (NMR) spectroscopy, diffusion-ordered spectroscopy (DOSY), temperature-dependent turbidimetry, isothermal titration calorimetry (ITC), and live time-lapse microscopy. NMR analysis revealed preferential methacrylation of C2 and C3 hydroxyl positions at low degrees of substitution, with increasing functionalization at the C4 position as the substitution degree increases. DOSY measurements further demonstrated distinct solvent- and substitution-dependent changes in polymer mobility under aqueous-phase-separating conditions. The lower critical solution temperature decreased as the Dex-MA concentration increased and shifted to higher temperatures with an increasing heating rate. Repeated thermal cycling progressively altered the transition temperature and reduced thermal hysteresis, particularly at higher concentrations, demonstrating a pronounced thermal-history dependence. ITC characterizations showed concentration- and temperature-dependent exothermic responses associated with polymer–solution interactions, while live imaging directly captured the progressive nucleation, growth, and coalescence of polymer-rich domains upon heating. Together, these findings establish molecular-to-mesoscale relationships linking chemical functionalization, polymer–solvent interactions, and thermodynamic–kinetic factors to the liquid–liquid phase separation of methacrylated polysaccharides, providing insights for the rational design of thermoresponsive polysaccharide-based biomaterials.
Related
- Quantitative proton density mapping with data-driven reception profile correction derived from macromolecular proton fraction
- A Structure-Based hERG Pose Selection Workflow Integrating Induced-Fit Docking, Shape Similarity, Interaction Fingerprints, and Molecular Dynamics
- A 16S rRNA-Based Screening Framework Reveals Distinct Microbial and Antimicrobial Resistance-Related Fingerprints in Aquaculture and Municipal Wastewater Effluents
- A comparison of artificial neural networks and partial least squares modelling for the rapid detection of the microbial spoilage of beef fillets based on Fourier transform infrared spectral fingerprints
- Protective Effects of Artemisia sphaerocephala Krasch Polysaccharide Against Polyethylene-Microplastic-Induced Intestinal and Testicular Injury in Male Mice
BibTeX
@article{moaseri2026macromolecular,
title = {{Macromolecular Fingerprints and Thermodynamic–Kinetic Regulation of Liquid–Liquid Phase Separation in Polysaccharide-Derived Biocondensates}},
author = {Erfan Moaseri and Patrick F. Strobel and Rabeya Sharmin Lima and Saniya Yesmin Bubli and Nazgol Behbahani and Haley A. Royce and Ella R. Cohen and Aylin Aykanat and Patricia M. Stone and Linqing Li},
journal = {JACS Au},
year = {2026},
month = oct,
doi = {10.1021/jacsau.6c01277},
url = {https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01277/5458560/Macromolecular-Fingerprints-and-Thermodynamic},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Macromolecular Fingerprints and Thermodynamic–Kinetic Regulation of Liquid–Liquid Phase Separation in Polysaccharide-Derived Biocondensates
AU - Erfan Moaseri
AU - Patrick F. Strobel
AU - Rabeya Sharmin Lima
AU - Saniya Yesmin Bubli
AU - Nazgol Behbahani
AU - Haley A. Royce
AU - Ella R. Cohen
AU - Aylin Aykanat
AU - Patricia M. Stone
AU - Linqing Li
PY - 2026
DA - 2026/10/26
JO - JACS Au
DO - 10.1021/jacsau.6c01277
UR - https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01277/5458560/Macromolecular-Fingerprints-and-Thermodynamic
AB - The relationship between chemical functionalization and the thermoresponsive phase separation of polysaccharide-derived biocondensates remains insufficiently investigated. In this study, we systematically examine how the substitution site, polymer concentration, solvent environment, and thermal history influence the phase behavior of methacrylated dextran derivatives using multidimensional nuclear magnetic resonance (NMR) spectroscopy, diffusion-ordered spectroscopy (DOSY), temperature-dependent turbidimetry, isothermal titration calorimetry (ITC), and live time-lapse microscopy. NMR analysis revealed preferential methacrylation of C2 and C3 hydroxyl positions at low degrees of substitution, with increasing functionalization at the C4 position as the substitution degree increases. DOSY measurements further demonstrated distinct solvent- and substitution-dependent changes in polymer mobility under aqueous-phase-separating conditions. The lower critical solution temperature decreased as the Dex-MA concentration increased and shifted to higher temperatures with an increasing heating rate. Repeated thermal cycling progressively altered the transition temperature and reduced thermal hysteresis, particularly at higher concentrations, demonstrating a pronounced thermal-history dependence. ITC characterizations showed concentration- and temperature-dependent exothermic responses associated with polymer–solution interactions, while live imaging directly captured the progressive nucleation, growth, and coalescence of polymer-rich domains upon heating. Together, these findings establish molecular-to-mesoscale relationships linking chemical functionalization, polymer–solvent interactions, and thermodynamic–kinetic factors to the liquid–liquid phase separation of methacrylated polysaccharides, providing insights for the rational design of thermoresponsive polysaccharide-based biomaterials.
SN - 2691-3704
ER -