华南理工大学边黎明团队近日揭示了设计者极简主义模型与相分离介导的细胞外基质组装和生物物理线索相似。相关论文发表在2025年6月9日出版的《自然-化学》杂志上。
受控液-液相分离和随后的定向相变的倾向对于凝聚介导的细胞外基质（ECM）组装至关重要。这种时空控制的ECM组装可用于开发基于凝聚层的聚合物组装策略，以产生可以模拟ECM复杂结构和生物物理线索的仿生材料。受原弹性蛋白结构的启发，研究组开发了一个由交替的疏水部分和共价交联结构域组成的设计师简约模型。
通过增加疏水部分的化合价和增强其相互作用强度，研究组可以控制组装程度以提高相分离的倾向，从而模拟原弹性蛋白的细胞外凝聚过程，包括液滴形成、聚结和成熟。随后的共价键触发凝聚层-水凝胶转变，增强组装顺序，以非均相水凝胶的形式稳定相分离结构，从而模拟共价交联衍生的弹性蛋白原纤化。此外，异质水凝胶网络建立了一个仿生基质，可以有效地促进贴壁干细胞的机械感知。
附：英文原文
Title: A designer minimalistic model parallels the phase-separation-mediated assembly and biophysical cues of extracellular matrix
Author: Xie, Xian, Li, Tianjie, Ma, Linjie, Wu, Jiahao, Qi, Yajing, Yang, Boguang, Li, Zhuo, Yang, Zhinan, Zhang, Kunyu, Chu, Zhiqin, Ngai, To, Xia, Jiang, Wang, Yi, Zhao, Pengchao, Bian, Liming
Issue&Volume: 2025-06-09
Abstract: The propensity for controlled liquid–liquid phase separation and subsequent directed phase transition are crucial for the coacervation-mediated assembly of extracellular matrix (ECM). This spatiotemporally controlled ECM assembly can be used to develop coacervate-based polymer assembly strategies to generate biomimetic materials that can emulate the complex structures and biophysical cues of the ECM. Inspired by the The propensity for controlled liquid–liquid phase separation and subsequent directed phase transition are crucial for the coacervation-mediated assembly of extracellular matrix (ECM). This spatiotemporally controlled ECM assembly can be used to develop coacervate-based polymer assembly strategies to generate biomimetic materials that can emulate the complex structures and biophysical cues of the ECM. Inspired by the tropoelastin structure, here we develop a designer minimalistic model consisting of alternating hydrophobic moieties and covalent crosslinking domains. By increasing the valence and enhancing the interaction strength of the hydrophobic moieties, we can control the degree of the assembly to enhance the propensity for phase separation and thus emulate the extracellular coacervation process of tropoelastin, including droplet formation, coalescence and maturation. The subsequent covalent-bonding-triggered coacervate–hydrogel transition with enhanced assembly order stabilizes the phase-separated structure in the form of a heterogeneous hydrogel, thereby mimicking covalent crosslinking-derived elastin fibrillation. Furthermore, the heterogeneous hydrogel network establishes a biomimetic matrix that can effectively promote the mechanosensing of adherent stem cells.
DOI: 10.1038/s41557-025-01837-5
