SIMPLE ENGINEERED BIOLOGICAL MOTIFS
FOR COMPLEX HYDROGEL FUNCTION
GOALS
This multidisciplinary team sits at the intersection of science and engineering, and seeks to establish the fundamental knowledge base needed to inspire cutting-edge practical applications of complex biological hydrogels. Such materials are abundantly used in nature, with properties that are unachieved by current synthetic materials. These include the ability to selectively filter complex solutions while retaining unique self-healing capabilities, to function as physical barriers that allow the penetration of bacteria while suppressing biofilm formation, and to maintain highly compressive states while providing a high level of lubrication. The goal of this IRG is to gain quantitative insight into, and predictive capability of, the molecular mechanisms that govern the unique structure and property combinations of complex biological hydrogels.
We will use this fundamental knowledge to guide the synthesis, fabrication and evaluation of next generation materials with potentially wide engineering implications, such as the design of self-healing filtration systems for water and food purification, new antimicrobial coatings for implants, or cartilage substitutes with high durability and lubrication capacity.
Current synthetic approaches are largely unable to recapitulate the sophisticated materials properties found in complex biological hydrogels. One reason for this is our lack of mechanistic understanding of the microscopic structures and chemistries that build and regulate natural hydrogels. This IRG will systematically analyze selected critical factors involved in complex biological hydrogel function, using an interdisciplinary set of tools that the investigators bring together, including the isolation and reconstitution of natural hydrogels, the chemical synthesis of bio-inspired polymers, molecular tools for controlling polymerization, and the state-of-the-art materials properties analysis, and molecular modeling. In particular, this IRG will focus on the study of three basic molecular elements that are found in complex biological hydrogels: a) conserved domains with repeating sequences, b) reversible/dynamic crosslinks, and c) variable glycosylation patterns.
 |
Katharina Ribbeck (co-leader) BioE |
|---|---|
 |
Bradley Olsen (co-leader) ChemE |
 |
Patrick Doyle Chem E |
 |
Niels Holten-Andersen DMSE |
 |
Jeremiah Johnson Chemistry |
 |
Alan Grodzinsky Bio E / EECS / Mech E |
 |
Paula Hammond Chem E |
 |
Timothy Lu EECS / Bio E |
 |
Gareth H. McKinley MechE |
HIGHLIGHTS
2020
Mucin Glycans Regulate Microbial Virulence
Thermally-Induced Surfactant Displacement to Induce Colloidal Gelation
2019
Enhanced diffusion by binding to the crosslinks of a polymer gel
The Gels, Elastomers, and Networks Experience (GENE)
2018
How Mucus Keeps You Healthy
The Gels, Elastomers, and Networks Experience (GENE)
2017
Understanding Loops in Polymer Networks Results in an Improved Theory for Rubbery Materials
Using Light to Control the Viscoelastic Mechanical Properties of Gel-Like Materials
2016
Biochemical mechanisms to control gel crosslinking and permeability
2015
Bio-Inspired Gels show promise as self-healing materials with properties controlled by metal ions
2020
Cheng, L.-C., Hashemnejad, S. M., Zarket, B., Muthukrishnan, S., and Doyle, P. S. “Thermally and PH-Responsive Gelation of Nanoemulsions Stabilized by Weak Acid Surfactants.” Journal of Colloid and Interface Science 563, (2020): 229–240. doi:10.1016/j.jcis.2019.12.054
Rasid, I.M., Ramirez, J., Olsen, B.D., and Holten-Andersen, N. "Understanding the molecular origin of shear thinning in associative polymers through quantification of bond dissociation under shear." Physical Review Materials, 4(5): Article 055602, May 2020. doi:10.1103/PhysRevMaterials.4.055602
2019
Samad, T., Co, J. Y., Witten, J., and Ribbeck, K. “Mucus and Mucin Environments Reduce the Efficacy of Polymyxin and Fluoroquinolone Antibiotics against Pseudomonas Aeruginosa” ACS Biomaterials Science & Engineering 5, no. 3 (2019): 1189–1194. doi:10.1021/acsbiomaterials.8b01054
Rajappan, A. and Mckinley, G. H. “Epidermal Biopolysaccharides from Plant Seeds Enable Biodegradable Turbulent Drag Reduction” Scientific Reports 9, no. 1 (2019): doi:10.1038/s41598-019-54521-3
Lai, E., Keshavarz, B., and Holten-Andersen, N. “Deciphering How the Viscoelastic Properties of Mussel-Inspired Metal-Coordinate Transiently Cross-Linked Gels Dictate Their Tack Behavior” Langmuir 35, no. 48 (2019): 15979–15984. doi:10.1021/acs.langmuir.9b02772
Wheeler, K. M., Cárcamo-Oyarce, G., Turner, B. S., Dellos-Nolan, S., Co, J. Y., Lehoux, S., Cummings, R. D., Wozniak, D. J., and Ribbeck, K. “Mucin Glycans Attenuate the Virulence of Pseudomonas Aeruginosa in Infection” Nature Microbiology 4, no. 12 (2019): 2146–2154. doi:10.1038/s41564-019-0581-8
Wang, J., Wang, R., Gu, Y., Sourakov, A., Olsen, B. D., and Johnson, J. A. “Counting Loops in Sidechain-Crosslinked Polymers from Elastic Solids to Single-Chain Nanoparticles.” Chemical Science, 10(20): 5332–5337, May 2019. <DOI:10.1039/c9sc01297d>
Chan, W.Y., King, E.J., and Olsen, B.D. “Hydrophobic and Bulk Polymerizable Protein-Based Elastomers Compatibilized with Surfactants.” ACS Sustainable Chemistry & Engineering, 7(10): 9103–9111, May 2019. <doi:10.1021/acssuschemeng.8b03557>
Inda, M. E., Broset, E., Lu, T. K., and Fuente-Nunez, C. D. L. “Emerging Frontiers in Microbiome Engineering” Trends in Immunology 40, no. 10 (2019): 952–973. doi:10.1016/j.it.2019.08.007
Inda, M. E., Mimee, M., and Lu, T. K. “Cell-Based Biosensors for Immunology, Inflammation, and Allergy” Journal of Allergy and Clinical Immunology 144, no. 3 (2019): 645–647. doi:10.1016/j.jaci.2019.07.024
Cazzell, S. A. and Holten-Andersen, N. “Expanding the Stoichiometric Window for Metal Cross-Linked Gel Assembly Using Competition” Proceedings of the National Academy of Sciences 116, no. 43 (2019): 21369–21374. doi:10.1073/pnas.1906349116
Cheng, L.-C., Sherman, Z. M., Swan, J. W., and Doyle, P. S. “Colloidal Gelation through Thermally Triggered Surfactant Displacement.” Langmuir, 35(29): 9464–9473, 2019. doi:10.1021/acs.langmuir.9b00596
Lamb, J. R., Qin, K. P., and Johnson, J. A. “Visible-Light-Mediated, Additive-Free, and Open-to-Air Controlled Radical Polymerization of Acrylates and Acrylamides” Polymer Chemistry, 10(13): 1585–1590, 2019. doi:10.1039 c9py00022d
Werlang, C., Carcarmo-Oyarce, G., and Ribbeck, K. "Engineering mucus to study and influence the microbiome." Nature Reviews Materials, 4(2): 134-145, February 2019. doi: 10.1038s41578-018-0079-7
Samad, T., Co, J.Y., Witten, J., and Ribbeck, K. “Mucus and Mucin Environments Reduce the Efficacy of Polymyxin and Fluoroquinolone Antibiotics against Pseudomonas aeruginosa.” ACS Biomaterials Science & Engineering, 5(3): 1189-1194, March 2019.
Witten, J., Samad, T., and Ribbeck, K. “Molecular Characterization of Mucus Binding.” Biomacromolecules, 20(4):1505–1513, 2019.
Cherstvy, A. G., Thapa, S., Wagner, C. E. , and Metzler, R. “Non-Gaussian, Non-Ergodic, and Non-Fickian Diffusion of Tracers in Mucin Hydrogels.” Soft Matter, 15(12): 2526–2551, March 2019.
2018
Gu, Y.W., Schauenburg, D., Bode, J.W., and Johnson, J.A. "Leaving Groups as Traceless Topological Modifiers for the Synthesis of Topologically Isomeric Polymer Networks." Journal of the American Chemical Society, 140(43): 14033-14037, October 2018. <DOI: 10.1021/jacs.8b07967>
Krishnan, Y. Rees, H.A., Rossitto, C.P., Kim, S.E., Hung, H.H.K., Frank, E.H., Olsen, B.D., Liu, D.R., Hammond, P.T., and Grodzinsky, A.J. "Green fluorescent proteins engineered for cartilage-targeted drug delivery: Insights for transport into highly charged avascular tissues." Biomaterials, 183: 218-233, November 2018. <DOI: 10.1016/j.biomaterials.2018.08.050>
Goodrich, C.P., Brenner, M.P., and Ribbeck, K. "Enhanced diffusion by binding to the crosslinks of a polymer gel." Nature Communications, 9 Article: 4348, October 2018.
Cheng, L.C., Godfrin, P., Swan, J.W., and Doyle, P.S. "Thermal processing of thermogelling nanoemulsions as a route to tune material properties." Soft Matter, 14(27): 5604-5614, July 2018.
Bansil, R. and Turner, B.S.* "The biology of mucus: composition, synthesis and organization." Advanced Drug Delivery Reviews, 124: 3-15, January 2018.
Sing, M.K., Burghardt, W.R., and Olsen, B.D. "Influence of end-block dynamics on deformation behavior of thermoresponsive elastin-like polypeptide hydrogels." Macromolecules, 51(8): 2951-2960, April 2018.
Cheng, L.C., Godfrin, P., Swan, J.W., and Doyle, P.S. "Thermal processing of thermogelling nanoemulsions as a route to tune material properties." Soft Matter, 14(27): 5604-5614, July 2018.
Gu, Y.W., Alt, E.A., Wang, H., Li, X.P., Willard, A.P., and Johnson, J.A. "Photoswitching topology in polymer networks with metal-organic cages as crosslinks." Nature, 560(7716): 65+, August 2018.
Kim, S., Peterson, A.M., and Holten-Andersen, N. "Enhanced water retention maintains energy dissipation in Dehydrated metal-coordinate polymer networks: Another role for Fe-catechol cross-links?" Chemistry of Materials, 30(11): 3648-3655, June 1018.
Witten, J., Samad, T., and Ribbeck, K. "Selective permeability of mucus barriers." Current Opinion in Biotechnology, 52: 124-133, August 2018.
Krishnan, Y. and Grodzinsky, A.J. "Cartilage diseases." Matrix Biology, SI 71-72: 51-69, October 2018. <DOI: 10.1016/j.matbio.2018.05.005>
Co, J.Y., Cárcamo-Oyarce, G., Billings, N., Wheeler, K.M., Grindy, S.C., Holten-Andersen, N. and Ribbeck, K. "Mucins trigger dispersal of Pseudomonas aeruginosa biofilms." Biofilms and Microbiomes, Article 23, October 2018. <DOI: 10.1038/s41522-018-0067-0>
Wagner, C., Wheeler, K., and Ribbeck, K. “Mucins and Their Role in Shaping the Functions of Mucus Barriers.” Annual Review of Cell and Developmental Biology, (34)1:189–215, 2018. <doi:10.1146/annurev-cellbio-100617-062818>
2017
Wagner, C.E., Turner, B.S., Rubinstein, M., McKinley, G.H., and Ribbeck, K. "A rheological study of the association and dynamics of MUC5AC gels." Biomacromolecules, 18(11): 3654-3664 SI, November 2017. DOI: 10.1021/acs.biomac.7b00809
Bajpayee, A.G., De la Vega, R.E., Scheu, M., Varady, N.H., Yannatos, I.A., Brown, L.A., Krishnan, Y., Fitzsimons, T.J., Bhattacharya, P., Frank, E.H., Grodzinsky, A.J., and Porter, R.M. “Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis.” European Cells & Materials, 34: 341-364, July-December 2017. DOI: 10.22203/eCM.v034a21
Cheng, L.C., Hsiao, L.C., and Doyle, P.S. “Multiple particle tracking study of thermally-gelling nanoemulsions.” Soft Matter, 13(37): 6606-6619, October 2017. DOI: 10.1039/c7sm01191a
Chen, L., Wang, K.X., and Doyle, P.S. “Effect of internal architecture on microgel deformation in microfluidic constrictions.” Soft Matter, 13(9): 1920-1928, 2017.DOI: 10.1039/c6sm02674e
Hsiao, L.C., Badruddoza, A.Z.M., Cheng, L.C., and Doyle, P.S. “3D printing of self-assembling thermoresponsive nanoemulsions into hierarchical mesostructured hydrogels.” Soft Matter, 13(5): 921-929, February 2017. DOI: 10.1039/c6sm02208
Kim, J.J., Bong, K.W., Reategui, E., Irimia, D., and Doyle, P.S. “Porous microwells for geometry-selective, large-scale microparticle arrays.” Nature Materials, 16(1): 139-146, January 2017. DOI: 10.1038/NMAT4747
Grindy, S.C. and Holten-Andersen, N. “Bio-inspired metal-coordinate hydrogels with Programmable viscoelastic material functions controlled by longwave UV light.” Soft Matter, 2017. DOI: 10.1039/c7sm00617a
Samad, T., Billings, N., Birjiniuk, A., Crouzier, T., Doyle, P.S. and Ribbeck, K. “Swimming bacteria promote dispersal of non-motile staphylococcal species.” International Society for Microbial Ecology Journal, 1-5: 1751-7362/17, April 2017. DOI: 10.1038/ismej.2017.23
Bajpayee, A.G., and Grodzinsky, A.J. “Cartilage-targeting drug delivery: Can electrostatic interactions help?” Nature Reviews Rheumatology, 13(3): 183-193, March 2017. DOI: 10.1038/nrrheum.2016.210
Grindy, S.C., Lenz, M., and Holten-Andersen, N. “Engineering elasticity and relaxation time in metal-coordinate cross-linked hydrogels.” Macromolecules, 49(21): 8306-8312, November 2016. DOI: 10.1021/acs.macromol.6b01523
Witten, J. and Ribbeck, K. “The particle in the spider's web: transport through biological hydrogels.” Nanoscale, 9(24): 8080-8095, June 2017. <DOI: 10.1039/c6nr09736g>
Samad, T., Billings, N., Birjiniuk, A., Crouzier, T., Doyle, P.S., and Ribbeck, K. “Swimming bacteria promote dispersal of non-motile staphylococcal species.” ISME Journal, 11(8): 1933-1937, August 2017. <DOI: 10.1038/ismej.2017.23>
Chen, W.G., Witten, J., Grindy, S.C., Holten-Andersen, N., and Ribbeck, K. “Charge Influences Substrate Recognition and Self-Assembly of Hydrophobic FG Sequences.“ Biophysical Journal, 113(9): 2088-2099, November 2017. <DOI: 10.1016/j.bpj.2017.08.058>
2016
Mozhdehi, D., Neal, J.A., Grindy, S.C., Cordeau, Y., Ayala, S., Holten-Andersen, N., and Guan, Z.B. “Tuning dynamic mechanical response in metallopolymer networks through simultaneous control of structural and temporal properties of the networks.” Macromolecules, 49(17): 6310-6321, September 2016. DOI: 10.1021/acs.macromol.6b01626
Tang, S.C. and Olsen, B.D. “Relaxation processes in supramolecular metallogels based on histidine-nickel coordination bonds.” Macromolecules, 49(23): 9163-9175, December 2016. DOI: 10.1021/acs.macromol.6b01618
Chen, L. An, H.Z., Haghgooie, R., Shank, A.T., Martel, J.M., Toner, M., and Doyle, P.S. “Flexible octopus-shaped hydrogel particles for specific cell capture.” Small, 12(15): 2001-2008, April 2016. DOI: 10.1002/smll.201600163
Tang, S.C., Habicht, A., Li, S.L., Seiffert, S., and Olsen, B.D. “Self-diffusion of associating star-shaped polymers.” Macromolecules, 49(15): 5599-5608, August 2016. DOI: 10.1021/acs.macromol.6b00959
Zhong, M.J., Wang, R., Kawamoto, K., Olsen, B.D., and Johnson, J.A. “Quantifying the impact of molecular defects on polymer network elasticity.” Science, 353(6305): 1264-1268, September 2016. DOI: 10.1126/science.aag0184
?>