Dynamic PEG-Peptide Hydrogels via Visible Light and FMN-Induced Tyrosine Dimerization.
Dynamic PEG-Peptide Hydrogels via Visible Light and FMN-Induced Tyrosine Dimerization.
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DOI：
10.1002/adhm.201800954
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发表时间：
2018-11
影响因子：
10
通讯作者：
Lin CC
中科院分区：
文献类型：
--
作者：
Liu HY;Nguyen HD;Lin CC
光响应水凝胶已经成为非常宝贵的三维（3D）培养基质，用于模拟细胞外基质（ECM）的各个方面。最近的研究主要集中在使用紫外线照射和多功能大分子在细胞存在的情况下诱导二次水凝胶交联和动态基质硬化。本文报道了通过黄素单核苷酸（FMN）诱导二酪氨酸交联设计一种新颖而简单的动态聚乙二醇-肽水凝胶体系。这些二酪氨酸键有效地增加了水凝胶交联密度和弹性模量。此外，在固定PEG大分子含量的情况下，水凝胶的硬化程度可以通过控制FMN浓度或肽连接体中酪氨酸残基的数量来调节。此外，含有酪氨酸的悬垂生化基序可以通过光掩膜控制光暴露在水凝胶网络中的时空模式。可见光和FMN诱导的酪氨酸二聚化过程产生细胞相容性和生理上相关的硬化程度，这可以从胰腺癌和基质细胞的细胞形态和基因表达的变化中看出。这种新的动态水凝胶方案对于寻求光响应水凝胶体系的研究人员来说是非常理想的，不需要复杂的化学合成和二次紫外光照射。采用正交光化学法制备了动态水凝胶体系。初级网络是通过模块化巯基-降冰片烯光点击反应交联的，而二级硬化是通过可见光诱导的二酪氨酸交联实现的。所有用于水凝胶交联和强化的成分都是市售的，这使得该系统非常适合研究时空调节的基质力学对细胞命运过程的影响。
Photo-responsive hydrogels have become invaluable three-dimensional (3D) culture matrices for mimicking aspects of extracellular matrix (ECM). Recent efforts have focused on using ultraviolet (UV) light exposure and multifunctional macromers to induce secondary hydrogel crosslinking and dynamic matrix stiffening in the presence of cells. This contribution reports the design of a novel yet simple dynamic poly(ethylene glycol)-peptide hydrogel system through flavin mononucleotide (FMN) induced di-tyrosine crosslinking. These di-tyrosine linkages effectively increase hydrogel crosslinking density and elastic modulus. In addition, the degree of stiffening in hydrogels at a fixed PEG macromer content can be readily tuned by controlling FMN concentration or the number of tyrosine residues built-in to the peptide linker. Furthermore, tyrosine-bearing pendant biochemical motifs could be spatial-temporally patterned in the hydrogel network via controlling light exposure through a photomask. The visible light and FMN induced tyrosine dimerization process produces cytocompatible and physiologically relevant degree of stiffening, as shown by changes of cell morphology and gene expression in pancreatic cancer and stromal cells. This new dynamic hydrogel scheme should be highly desirable for researchers seeking a photo-responsive hydrogel system without complicated chemical synthesis and secondary UV light irradiation. A dynamic hydrogel system is prepared using orthogonal photochemistry. The primary network is crosslinked by modular thiol-norbornene photoclick reaction, whereas the secondary stiffening is achieved via visible light induced di-tyrosine crosslinking. All components used in hydrogel crosslinking and stiffening are commercially available, making the system highly adaptable for studying the effect of spatial-temporally regulated matrix mechanics on cell fate processes.
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DOI：
10.1039/c6ib00027d
发表时间：
2016-06-13
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Caliari SR;Perepelyuk M;Soulas EM;Lee GY;Wells RG;Burdick JA
通讯作者：
Burdick JA
影响因子：
3.4
作者：
Fiedler CI;Aisenbrey EA;Wahlquist JA;Heveran CM;Ferguson VL;Bryant SJ;McLeod RR
通讯作者：
McLeod RR
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA
影响因子：
14
作者：
Liu HY;Korc M;Lin CC
通讯作者：
Lin CC
影响因子：
29.4
作者：
Fairbanks, Benjamin D;Schwartz, Michael P;Halevi, Alexandra E;Nuttelman, Charles R;Bowman, Christopher N;Anseth, Kristi S
通讯作者：
Anseth, Kristi S