Engineering the Dynamic Properties of Protein Networks through Sequence Variation
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The dynamic behavior of macromolecular networks dominates the mechanical properties of soft materials and influences biological processes at multiple length scales. In hydrogels prepared from self-assembling artificial proteins, stress relaxation and energy dissipation arise from the transient character of physical network junctions. Here we show that subtle changes in sequence can be used to program the relaxation behavior of end-linked networks of engineered coiled-coil proteins. Single-site substitutions in the coiled-coil domains caused shifts in relaxation time over 5 orders of magnitude as demonstrated by dynamic oscillatory shear rheometry and stress relaxation measurements. Networks with multiple relaxation time scales were also engineered. This work demonstrates how time-dependent mechanical responses of macromolecular materials can be encoded in genetic information.
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Recombinant proteins are molecularly well-defined and can be tuned independently for stiffness, viscoelastic behavior, and chemical functionality.
“Recombinant proteins are molecularly well-defined and can be tuned independently for stiffness, viscoelastic behavior, and chemical functionality203–205.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [205]
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Cites
Ellman, G. L. (1959) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(59)90090-6 · Cited by 26,383 · see citing works
Matrix elasticity directs stem cell lineage specification
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.044 · Cited by 13,915 · see citing works
Rubinstein, M., & Colby, R. H. (2003) · doi:10.1093/oso/9780198520597.001.0001 · Cited by 5,686 · see citing works
Cell locomotion and focal adhesions are regulated by substrate flexibility.
Pelham, R., & Wang, Y.-L. (1997) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.94.25.13661 · Cited by 3,156 · see citing works
Hydrogels with tunable stress relaxation regulate stem cell fate and activity
Chaudhuri, O., Gu, L., Klumpers, D., Darnell, M., Bencherif, S. A., Weaver, J. C., Huebsch, N., Lee, H.-P., Lippens, E., Duda, G. N., et al. (2016) · Nature Materials · doi:10.1038/nmat4489 · Cited by 2,443 · see citing works
Reversible Polymers Formed from Self-Complementary Monomers Using Quadruple Hydrogen Bonding
Sijbesma, R. P., Beijer, F. H., Brunsveld, L., Folmer, B. J. B., Hirschberg, J. H. K. K., Lange, R. F. M., Lowe, J. K. L., & Meijer, E. W. (1997) · Science · doi:10.1126/science.278.5343.1601 · Cited by 2,396 · see citing works
Multi-scale multi-mechanism design of tough hydrogels: building dissipation into stretchy networks
Zhao, X. (2013) · Soft Matter · doi:10.1039/c3sm52272e · Cited by 1,254 · see citing works
Materials selection in mechanical design
Ashby, M., & CEBON, D. (1993) · Journal de Physique IV (Proceedings) · doi:10.1051/jp4:1993701 · Cited by 1,116 · see citing works
Reversible Hydrogels from Self-Assembling Artificial Proteins
Petka, W. A., Harden, J. L., McGrath, K. P., Wirtz, D., & Tirrell, D. A. (1998) · Science · doi:10.1126/science.281.5375.389 · Cited by 1,076 · see citing works
Self-citationDynamic urea bond for the design of reversible and self-healing polymers
Ying, H., Zhang, Y., & Cheng, J. (2014) · Nature Communications · doi:10.1038/ncomms4218 · Cited by 987 · see citing works
Interior and surface of monomeric proteins
Miller, S., Janin, J., Lesk, A. M., & Chothia, C. (1987) · Journal of Molecular Biology · doi:10.1016/0022-2836(87)90038-6 · Cited by 952 · see citing works
Substrate stress relaxation regulates cell spreading
Chaudhuri, O., Gu, L., Darnell, M., Klumpers, D. D., Bencherif, S. A., Weaver, J. C., Huebsch, N., & Mooney, D. J. (2015) · Nature Communications · doi:10.1038/ncomms7365 · Cited by 887 · see citing works
Annable, T., Buscall, R., Ettelaie, R., et al. (1993) · Journal of Rheology · doi:10.1122/1.550391 · Cited by 793 · see citing works
Adaptable Hydrogel Networks with Reversible Linkages for Tissue Engineering
Wang, H., & Heilshorn, S. C. (2015) · Advanced Materials · doi:10.1002/adma.201501558 · Cited by 722 · see citing works
Lutolf, M. P., & Hubbell, J. A. (2003) · Biomacromolecules · doi:10.1021/bm025744e · Cited by 679 · see citing works
Substrate flexibility regulates growth and apoptosis of normal but not transformed cells
Wang, H.-B., Dembo, M., & Wang, Y. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.279.5.c1345 · Cited by 655 · see citing works
Control of hierarchical polymer mechanics with bioinspired metal-coordination dynamics
Grindy, S. C., Learsch, R. W., Mozhdehi, D., Cheng, J., Barrett, D. G., Guan, Z., Messersmith, P. B., & Holten‐Andersen, N. (2015) · Nature Materials · doi:10.1038/nmat4401 · Cited by 510 · see citing works
Crosslinked poly(vinyl alcohol) hydrogels as swollen elastic networks
Peppas, N. A., & Merrill, E. W. (1977) · Journal of Applied Polymer Science · doi:10.1002/app.1977.070210704 · Cited by 445 · see citing works
The influence of substrate creep on mesenchymal stem cell behaviour and phenotype
Cameron, A. R., Frith, J. E., & Cooper-White, J. J. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.04.003 · Cited by 428 · see citing works
McKinnon, D. D., Domaille, D. W., Cha, J. N., & Anseth, K. S. (2013) · Advanced Materials · doi:10.1002/adma.201303680 · Cited by 417 · see citing works
The elastic modulus of Matrigel™ as determined by atomic force microscopy
Soofi, S. S., Last, J. A., Liliensiek, S. J., Nealey, P. F., & Murphy, C. J. (2009) · Journal of Structural Biology · doi:10.1016/j.jsb.2009.05.005 · Cited by 309 · see citing works
Mussel-Inspired Histidine-Based Transient Network Metal Coordination Hydrogels
Fullenkamp, D. E., He, L., Barrett, D. G., et al. (2013) · Macromolecules · doi:10.1021/ma301791n · Cited by 309 · see citing works
The Crystal Structure of a Five-Stranded Coiled Coil in COMP: A Prototype Ion Channel?
Malashkevich, V. N., Kammerer, R. A., Efimov, V. P., Schulthess, T., & Engel, J. (1996) · Science · doi:10.1126/science.274.5288.761 · Cited by 301 · see citing works
Tuning the erosion rate of artificial protein hydrogels through control of network topology
Shen, W., Zhang, K., Kornfield, J. A., & Tirrell, D. A. (2006) · Nature Materials · doi:10.1038/nmat1573 · Cited by 294 · see citing works
Self-citationMcPherson, D. T., Xu, J., & Urry, D. W. (1996) · Protein Expression and Purification · doi:10.1006/prep.1996.0008 · Cited by 253 · see citing works
Yielding Behavior in Injectable Hydrogels from Telechelic Proteins
Olsen, B. D., Kornfield, J. A., & Tirrell, D. A. (2010) · Macromolecules · doi:10.1021/ma101434a · Cited by 207 · see citing works
Self-citationReversible Hydrogels from Self-Assembling Genetically Engineered Protein Block Copolymers
Xu, C., Breedveld, V., & Kopec̆ek, J. (2005) · Biomacromolecules · doi:10.1021/bm050017f · Cited by 171 · see citing works
Kinetics of Folding of Leucine Zipper Domains
Wendt, H., Berger, C. E. M., Baici, A., Thomas, R. M., & Bosshard, H. R. (1995) · Biochemistry · doi:10.1021/bi00012a028 · Cited by 147 · see citing works
Anomalous Self-Diffusion and Sticky Rouse Dynamics in Associative Protein Hydrogels
Tang, S., Wang, M., & Olsen, B. D. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b00722 · Cited by 142 · see citing works
Rational Control of Viscoelastic Properties in Multicomponent Associative Polymer Networks
Loveless, D. M., Jeon, S. L., & Craig, S. L. (2005) · Macromolecules · doi:10.1021/ma0518611 · Cited by 128 · see citing works
Programming Molecular Association and Viscoelastic Behavior in Protein Networks
Dooling, L. J., Buck, M. E., Zhang, W., & Tirrell, D. A. (2016) · Advanced Materials · doi:10.1002/adma.201506216 · Cited by 103 · see citing works
Self-citationSubstrate Viscosity Enhances Correlation in Epithelial Sheet Movement
Murrell, M. P., Kamm, R. D., & Matsudaira, P. T. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.05.048 · Cited by 102 · see citing works
Shen, W. H., Kornfield, J. A., & Tirrell, D. A. (2006) · Soft Matter · doi:10.1039/b610986a · Cited by 87 · see citing works
Self-citationGunasekar, S. K., Asnani, M., Limbad, C., et al. (2009) · Biochemistry · doi:10.1021/bi900534r · Cited by 86 · see citing works
Efimov, V. P., Lustig, A., & Engel, J. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)80239-4 · Cited by 81 · see citing works
Measuring cellular forces using bis-aliphatic hydrazone crosslinked stress-relaxing hydrogels
McKinnon, D. D., Domaille, D. W., Brown, T. E., Kyburz, K. A., Kiyotake, E. A., Cha, J. N., & Anseth, K. S. (2014) · Soft Matter · doi:10.1039/c4sm01365d · Cited by 80 · see citing works
Molecular structure and elastic behavior of poly(ethylene oxide) networks swollen to equilibrium
Gnanou, Y., Hild, G., & Rempp, P. F. (1987) · Macromolecules · doi:10.1021/ma00173a037 · Cited by 69 · see citing works
Energy transfer analysis of Fos-Jun dimerization and DNA binding.
Patel, L. R., Curran, T., & Kerppola, T. K. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.15.7360 · Cited by 67 · see citing works
Menyo, M. S., Hawker, C. J., & Waite, J. H. (2015) · ACS Macro Letters · doi:10.1021/acsmacrolett.5b00664 · Cited by 64 · see citing works
Shen, W. H., Kornfield, J. A., & Tirrell, D. A. (2007) · Macromolecules · doi:10.1021/ma0615194 · Cited by 63 · see citing works
Self-citationRheological monitoring of long-term degrading polymer hydrogels
Meyvis, T. K. L., Smedt, S. C. D., Demeester, J., & Hennink, W. E. (1999) · Journal of Rheology · doi:10.1122/1.551012 · Cited by 56 · see citing works
Guo, Y., Kammerer, R. A., & Engel, J. (2000) · Biophysical Chemistry · doi:10.1016/s0301-4622(00)00119-8 · Cited by 26 · see citing works
Park, S.-Y., Quezada, C. M., Bilwes, A. M., et al. (2004) · Biochemistry · doi:10.1021/bi0352419 · Cited by 26 · see citing works
In Situ Forming Physical Hydrogels for Three‐dimensional Tissue Morphogenesis
Liu, Y., Liu, B., Riesberg, J. J., et al. (2011) · Macromolecular Bioscience · doi:10.1002/mabi.201100119 · Cited by 25 · see citing works
The kinetics of chain exchange in two‐chain coiled coils: αα‐ and ββ‐tropomyosin
Ozeki, S., Kato, T., Holtzer, M. E., et al. (1991) · Biopolymers · doi:10.1002/bip.360310805 · Cited by 18 · see citing works
Terskikh, A. V., Potekhin, S. A., Melnik, T. N., & Kajava, A. V. (1997) · International Journal of Peptide Research and Therapeutics · doi:10.1007/bf02442893 · Cited by 6 · see citing works
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Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works
Fabrication of Bioinspired Hydrogels: Challenges and Opportunities
Fan, H., & Gong, J. P. (2020) · Macromolecules · doi:10.1021/acs.macromol.0c00238 · Cited by 292 · see citing works
- Authors
- Dooling, L. J., & Tirrell, D. A.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Tirrell, David A.
- Venue
- ACS Central Science
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-10-18
- Volume
- 2
- Issue
- 11
- Pages
- 812-819
- ISSN
- 2374-7943 (ISSN-L)
- 2374-7951
- PMC
- PMC5126713
- OpenAlex
- W2533589637
- Cited by
- 63
- References
- 46
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 8 · 2019: 11 · 2018: 7 · 2017: 3
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- ACS Central Science (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (DMR-1506483)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Physical Sciences › Engineering › Mechanical Engineering › Advanced Materials and Mechanics
- Keywords
- coiled-coil proteins, engineered proteins, protein hydrogels, stress relaxation, relaxation time, sequence variation, dynamic mechanical properties, protein self-assembly, soft materials
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