Photo-Dimerization Induced Dynamic Viscoelastic Changes in ABA Triblock Copolymer-Based Hydrogels for 3D Cell Culture

Cells sense and respond not only to biochemical signals but also to biophysical signals (e.g., matrix elasticity). In addition to matrix elasticity, recent studies have revealed that viscoelasticity (e.g., stress relaxation) significantly affects cellular functions, such as spreading, proliferation, and differentiation. Herein, we describe a cytocompatible and dynamic hydrogel that is comprised of well-defined ABA triblock copolymers, which enable significant changes of viscoelastic properties solely by UV light irradiation. The A block contains N-isopropylacrylamide and an acrylate monomer with a coumarin side chain, whereas the B block is biocompatible poly(ethylene oxide). The triblock copolymer forms a physically cross-linked hydrogel under physiologically relevant conditions. However, under UV light irradiation, the viscoelasticity of the hydrogel is dynamically modulated due to the photodimerization of coumarin moieties. After UV illumination, rheological properties of the hydrogel are drastically d...

[1]  James C. Weaver,et al.  Hydrogels with tunable stress relaxation regulate stem cell fate and activity , 2015, Nature materials.

[2]  James C. Weaver,et al.  Substrate stress relaxation regulates cell spreading , 2015, Nature Communications.

[3]  Z. Werb,et al.  Remodelling the extracellular matrix in development and disease , 2014, Nature Reviews Molecular Cell Biology.

[4]  Kei Saito,et al.  Photo-reversible dimerisation reactions and their applications in polymeric systems , 2014 .

[5]  Kristi S. Anseth,et al.  Mechanical memory and dosing influence stem cell fate , 2014, Nature materials.

[6]  Guillermo A. Gomez,et al.  The effect of time-dependent deformation of viscoelastic hydrogels on myogenic induction and Rac1 activity in mesenchymal stem cells. , 2014, Biomaterials.

[7]  K. Anseth,et al.  Biophysically Defined and Cytocompatible Covalently Adaptable Networks as Viscoelastic 3D Cell Culture Systems , 2014, Advances in Materials.

[8]  Fiona M. Watt,et al.  Role of the extracellular matrix in regulating stem cell fate , 2013, Nature Reviews Molecular Cell Biology.

[9]  T. Lodge,et al.  High toughness, high conductivity ion gels by sequential triblock copolymer self-assembly and chemical cross-linking. , 2013, Journal of the American Chemical Society.

[10]  Wesley R. Legant,et al.  Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels , 2013, Nature materials.

[11]  T. Lodge,et al.  Light-controlled reversible micellization of a diblock copolymer in an ionic liquid , 2012 .

[12]  T. Lodge,et al.  Thermoreversible high-temperature gelation of an ionic liquid with poly(benzyl methacrylate-b-methyl methacrylate-b-benzyl methacrylate) triblock copolymer , 2012 .

[13]  Brendon M. Baker,et al.  Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues , 2012, Journal of Cell Science.

[14]  D. Seliktar.  Designing Cell-Compatible Hydrogels for Biomedical Applications , 2012, Science.

[15]  Yue Zhao,et al.  Light-Responsive Block Copolymer Micelles , 2012 .

[16]  Z. Werb,et al.  The extracellular matrix: A dynamic niche in cancer progression , 2012, The Journal of cell biology.

[17]  Murat Guvendiren,et al.  Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics , 2012, Nature Communications.

[18]  T. Lodge,et al.  Viscoelastic Properties, Ionic Conductivity, and Materials Design Considerations for Poly(styrene-b-ethylene oxide-b-styrene)-Based Ion Gel Electrolytes , 2011 .

[19]  L. Benyahia,et al.  Structure and Rheology of Self-Assembled Telechelic Associative Polymers in Aqueous Solution before and after Photo-Cross-Linking , 2011 .

[20]  Justin Cooper-White,et al.  The influence of substrate creep on mesenchymal stem cell behaviour and phenotype. , 2011, Biomaterials.

[21]  Hans Clevers,et al.  Actomyosin-Mediated Cellular Tension Drives Increased Tissue Stiffness and β-Catenin Activation to Induce Epidermal Hyperplasia and Tumor Growth. , 2024, Cancer cell.

[22]  Bin Zhao,et al.  Rheological properties of aqueous micellar gels of a thermo- and pH-sensitive ABA triblock copolymer. , 2011, The journal of physical chemistry. B.

[23]  Fernanda F. Rossetti,et al.  Quantitative evaluation of mechanosensing of cells on dynamically tunable hydrogels. , 2011, Journal of the American Chemical Society.

[24]  Luc Tremblay,et al.  Both core- and shell-cross-linked nanogels: photoinduced size change, intraparticle LCST, and interparticle UCST thermal behaviors. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[25]  Valerie M. Weaver,et al.  The extracellular matrix at a glance , 2010, Journal of Cell Science.

[26]  David J. Mooney,et al.  Harnessing Traction-Mediated Manipulation of the Cell-Matrix Interface to Control Stem Cell Fate , 2010, Nature materials.

[27]  Zhigang Suo,et al.  Stress-relaxation behavior in gels with ionic and covalent crosslinks. , 2010, Journal of applied physics.

[28]  Samuel K Sia,et al.  Dynamic Hydrogels: Switching of 3D Microenvironments Using Two‐Component Naturally Derived Extracellular Matrices , 2010, Advanced materials.

[29]  Mikala Egeblad,et al.  Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling , 2009, Cell.

[30]  Paul A. Janmey,et al.  Cell-Cycle Control by Physiological Matrix Elasticity and In Vivo Tissue Stiffening , 2009, Current Biology.

[31]  Ravi S Kane,et al.  The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells. , 2009, Biomaterials.

[32]  Mark W. Tibbitt,et al.  Hydrogels as extracellular matrix mimics for 3D cell culture. , 2009, Biotechnology and bioengineering.

[33]  Jason A. Burdick,et al.  Sequential crosslinking to control cellular spreading in 3-dimensional hydrogels , 2009 .

[34]  Kristi S. Anseth,et al.  Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties , 2009, Science.

[35]  C. Cho,et al.  Regulation of cellular morphology using temperature-responsive hydrogel for integrin-mediated mechanical force stimulation. , 2009, Biomaterials.

[36]  Albert J. Keung,et al.  Substrate modulus directs neural stem cell behavior. , 2008, Biophysical journal.

[37]  A. Crosby,et al.  Photo-cross-linked PLA-PEO-PLA hydrogels from self-assembled physical networks: mechanical properties and influence of assumed constitutive relationships. , 2008, Biomacromolecules.

[38]  C. McCormick,et al.  Thermoreversible hydrogels from RAFT-synthesized BAB triblock copolymers: steps toward biomimetic matrices for tissue regeneration. , 2008, Biomacromolecules.

[39]  P. Janmey,et al.  Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[40]  X. Jiang,et al.  Facile Fabrication of Reversible Core Cross-Linked Micelles Possessing Thermosensitive Swellability , 2007 .

[41]  B. Qi,et al.  Polymer Micelles Stabilization on Demand through Reversible Photo-Cross-Linking , 2007 .

[42]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[43]  V. Monnier,et al.  Cross‐Linking of the Extracellular Matrix by the Maillard Reaction in Aging and Diabetes: An Update on “a Puzzle Nearing Resolution” , 2005, Annals of the New York Academy of Sciences.

[44]  S. Armes,et al.  Synthesis and characterization of biocompatible thermo-responsive gelators based on ABA triblock copolymers. , 2005, Biomacromolecules.

[45]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[46]  Adam J. Engler,et al.  Myotubes differentiate optimally on substrates with tissue-like stiffness , 2004, The Journal of cell biology.

[47]  J. Hubbell,et al.  Towards a fully-synthetic substitute of alginate: development of a new process using thermal gelation and chemical cross-linking. , 2004, Biomaterials.

[48]  B. Love,et al.  Coumarins in polymers: from light harvesting to photo-cross-linkable tissue scaffolds. , 2004, Chemical reviews.

[49]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[50]  J. Hubbell,et al.  Materials for Cell Encapsulation via a New Tandem Approach Combining Reverse Thermal Gelation and Covalent Crosslinking. , 2002 .

[51]  Allen J. Bailey,et al.  Molecular mechanisms of ageing in connective tissues , 2001, Mechanisms of Ageing and Development.

[52]  I. Wilson,et al.  Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. , 2000, European journal of biochemistry.

[53]  Y. Wang,et al.  Cell locomotion and focal adhesions are regulated by substrate flexibility. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[54]  R. Tyrrell,et al.  OXYGEN‐DEPENDENCE OF NEAR UV (365 NM) LETHALITY AND THE INTERACTION OF NEAR UV AND X‐RAYS IN TWO MAMMALIAN CELL LINES , 1976, Photochemistry and photobiology.

[55]  Dennis E. Koppel,et al.  Analysis of Macromolecular Polydispersity in Intensity Correlation Spectroscopy: The Method of Cumulants , 1972 .

[56]  Yujie Ma,et al.  25th Anniversary Article: Designer Hydrogels for Cell Cultures: A Materials Selection Guide , 2014, Advanced materials.

[57]  Masato Mikami,et al.  A Synthetic Hydrogel with Thermoreversible Gelation. I. Preparation and Rheological Properties , 1994 .

[58]  Roald Hoffmann,et al.  Stereochemistry of Electrocyclic Reactions (福井謙一とフロンティア軌導理論) -- (参考論文) , 1965 .