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
Bradley Olsen
Patrick Doyle
Chem E
Niels Holten-Andersen
Jeremiah Johnson
Alan Grodzinsky
Bio E / EECS / Mech E
Paula Hammond
Chem E
Timothy Lu
EECS / Bio E
Gareth H. McKinley


Mucin Glycans Regulate Microbial Virulence

Thermally-Induced Surfactant Displacement to Induce Colloidal Gelation

Enhanced diffusion by binding to the crosslinks of a polymer gel

The Gels, Elastomers, and Networks Experience (GENE)

How Mucus Keeps You Healthy

The Gels, Elastomers, and Networks Experience (GENE)

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

Biochemical mechanisms to control gel crosslinking and permeability

Bio-Inspired Gels show promise as self-healing materials with properties controlled by metal ions





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


Samad, T., Co, J. Y., Witten, J., and Ribbeck, K. “Mucus and Mucin Environments Reduce the Efficacy of Polymyxin and Fluoroquinolone Antibiotics against Pseudomonas AeruginosaACS 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 ReductionScientific 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 BehaviorLangmuir 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 InfectionNature 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 EngineeringTrends in Immunology 40, no. 10 (2019): 952–973. doi:10.1016/

Inda, M. E., Mimee, M., and Lu, T. K. “Cell-Based Biosensors for Immunology, Inflammation, and AllergyJournal 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 AcrylamidesPolymer 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.

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>

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>


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