Eric Appel, Postdoctoral Faculty Sponsor
Diels-Alder Photoclick Patterning of Extracellular Matrix for Spatially Controlled Cell Behaviors
Strategies that mimic the spatial complexity of natural tissues can provide cellular scaffolds to probe fundamental questions in cell biology and offer new materials for regenerative medicine. Here, the authors demonstrate a light-guided patterning platform that uses natural engineered extracellular matrix (ECM) proteins as a substrate to program cellular behaviors. A photocaged diene which undergoes Diels-Alder-based click chemistry upon uncaging with 365 nm light is utilized. By interfacing with commercially available maleimide dienophiles, patterning of common ECM proteins (collagen, fibronectin Matrigel, laminin) with readily purchased functional small molecules and growth factors is achieved. Finally, the use of this platform to spatially control ERK activity and migration in mammalian cells is highlighted, demonstrating programmable cell behavior through patterned chemical modification of natural ECM.
View details for DOI 10.1002/adma.202303453
View details for Web of Science ID 001082545700001
View details for PubMedID 37611189
Design, Synthesis, and Application of a Water-soluble Photocage for Aqueous Cyclopentadiene-based Diels-Alder Photoclick Chemistry in Hydrogels.
Angewandte Chemie (International ed. in English)
Spatiotemporally functionalized hydrogels have exciting applications in tissue engineering, but their preparation often relies on radical-based strategies that can be deleterious in biological settings. Herein, the computationally guided design, synthesis, and application of a water-soluble cyclopentadienone-norbornadiene (CPD-NBD) adduct is disclosed as a diene photocage for radical-free Diels-Alder photopatterning. We show that this scalable CPD-NBD derivative is readily incorporated into hydrogel formulations, providing gels that can be patterned with dienophiles upon 365 nm uncaging of cyclopentadiene. Patterning is first visualized through conjugation of cyanine dyes, then biological utility is highlighted by patterning peptides to direct cellular adhesion. Finally, the ease of use and versatility of this CPD-NBD derivative is demonstrated by direct incorporation into a commercial 3D printing resin to enable the photopatterning of structurally complex, printed hydrogels.
View details for DOI 10.1002/anie.202301157
View details for PubMedID 36821552
Controlled Diels-Alder "Click" Strategy to Access Mechanically Aligned Main-Chain Liquid Crystal Networks
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2023; 62 (1): e202214339
Aligned liquid crystal polymers are materials of interest for electronic, optic, biological and soft robotic applications. The manufacturing and processing of these materials have been widely explored with mechanical alignment establishing itself as a preferred method due to its ease of use and widespread applicability. However, the fundamental chemistry behind the required two-step polymerization for mechanical alignment has limitations in both fabrication and substrate compatibility. In this work we introduce a new protection-deprotection approach utilizing a two-stage Diels-Alder cyclopentadiene-maleimide step-growth polymerization to enable mild yet efficient, fast, controlled, reproducible and user-friendly polymerizations, broadening the scope of liquid crystal systems. Thorough characterization of the films by DSC, DMA, POM and WAXD show the successful synthesis of a uniaxially aligned liquid crystal network with thermomechanical actuation abilities.
View details for DOI 10.1002/anie.202214339
View details for Web of Science ID 000924284100047
View details for PubMedID 36315038
Rational mechanochemical design of Diels-Alder crosslinked biocompatible hydrogels with enhanced properties
2022; 9 (7): 1947-1953
An important but often overlooked feature of Diels-Alder (DA) cycloadditions is the ability for DA adducts to undergo mechanically induced cycloreversion when placed under force. Herein, we demonstrate that the commonly employed DA cycloaddition between furan and maleimide to crosslink hydrogels results in slow gelation kinetics and "mechanolabile" crosslinks that relate to reduced material strength. Through rational computational design, "mechanoresistant" DA adducts were identified by constrained geometries simulate external force models and employed to enhance failure strength of crosslinked hydrogels. Additionally, utilization of a cyclopentadiene derivative, spiro[2.4]hepta-4,6-diene, provided mechanoresistant DA adducts and rapid gelation in minutes at room temperature. This study illustrates that strategic molecular-level design of DA crosslinks can provide biocompatible materials with improved processing, mechanical durability, lifetime, and utility.
View details for DOI 10.1039/d2mh00338d
View details for Web of Science ID 000795996400001
View details for PubMedID 35575385