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Liquid–liquid phase separation of proteins and peptides derived from biological materials: Discovery, protein engineering, and emerging applications

Published online by Cambridge University Press:  10 December 2020

Yue Sun ,
Zhi Wei Lim ,
Qi Guo ,
Jing Yu  and
Ali Miserez
Yue Sun
Affiliation:
Nanyang Technological University, Singapore; yue006@e.ntu.edu.sg
Zhi Wei Lim
Affiliation:
Nanyang Technological University, Singapore; zwlim@ntu.edu.sg
Qi Guo
Affiliation:
Nanyang Technological University, Singapore; guoq0005@e.ntu.edu.sg
Jing Yu
Affiliation:
Nanyang Technological University, Singapore; yujing@ntu.edu.sg
Ali Miserez
Affiliation:
Nanyang Technological University, Singapore; ali.miserez@ntu.edu.sg
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Abstract

Biological materials represent a major source of inspiration to engineer protein-based polymers that can replicate the properties of living systems. Combined with our ability to control the molecular structure of proteins at the single amino acid level, this results in a vast array of attractive possibilities for materials science, an interest that is undeniably related to simplified procedures in gene synthesis, cloning, and biotechnological production. In parallel, it has been increasingly appreciated that living organisms exploit liquid–liquid phase separation (LLPS) to fabricate extracellular structures. In this article, we discuss the central role of protein LLPS in the fabrication of selected biological structures, including biological adhesives and hard biomolecular composites, and how physicochemical lessons from these systems are being replicated in synthetic analogs. Recent translational applications of protein LLPS are highlighted, notably aqueous-resistant adhesives, stimuli-responsive therapeutics carriers, and matrix materials for green structural composites.

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Type
Engineered Proteins as Multifunctional Materials
Information
MRS Bulletin , Volume 45 , Issue 12: Engineered Proteins as Multifunctional Materials , December 2020 , pp. 1039 - 1047
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Copyright
Copyright © The Author(s), 2020, published on behalf of Materials Research Society by Cambridge University Press

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References

Weis-Fogh, T., J. Exp. Biol. 37, 889 (1960).Google Scholar
Elvin, C.M., Carr, A.G., Huson, M.G., Maxwell, J.M., Pearson, R.D., Vuocolo, T., Liyou, N.E., Wong, D.C.C., Merritt, D.J., Dixon, N.E., Nature 437, 999 (2005).Google Scholar
Li, L., Luo, T., Kiick, K.L., Macromol. Rapid Commun. 36, 90 (2015).Google Scholar
Brown, T.A., Gene Cloning and DNA Analysis: An Introduction, 6th ed. (Wiley, Hoboken, NJ, 2016).Google Scholar
Tokareva, O., Michalczechen-Lacerda, V.A., Rech, E.L., Kaplan, D.L., Microb. Biotechnol. 6, 651 (2013).CrossRefGoogle Scholar
Yeo, G.C., Aghaei-Ghareh-Bolagh, B., Brackenreg, E.P., Hiob, M.A., Lee, P., Weiss, A.S., Adv. Healthc. Mater. 4, 2530 (2015).CrossRefGoogle Scholar
Heidebrecht, A., Scheibel, T., in Advances in Applied Microbiology, Sariaslani, S., Gadd, Eds., G.M. (Academic Press, Cambridge, MA, 2013), vol. 82, pp. 115–153.Google Scholar
Yang, Y.J., Holmberg, A.L., Olsen, B.D., Annu. Rev. Chem. Biomol. Eng. 8, 549 (2017).10.1146/annurev-chembioeng-060816-101620CrossRefGoogle Scholar
Brangwynne, C.P., Tompa, P., Pappu, R.V., Nat. Phys. 11, 899 (2015).CrossRefGoogle Scholar
Dignon, G.L., Zheng, W., Mittal, J., Curr. Opin. Chem. Eng. 23, 92 (2019).CrossRefGoogle Scholar
Bungenberg de Jong, H.G., Kruyt, H.R., in Colloid Science, Kruyt, Ed., H.R. (Elsevier, Amsterdam, The Netherlands, 1949), vol. 2, pp. 433–482.Google Scholar
Cooper, C.L. P.L. Dubin, A.B. Kayitmazer, S. Turksen, Curr. Opin. Colloid Interface Sci. 10, 52 (2005).CrossRefGoogle Scholar
Shin, Y., Brangwynne, C.P., Science 357, eaaf4382 (2017).CrossRefGoogle Scholar
Muiznieks, L.D., Sharpe, S., Pomès, R., Keeley, F.W., J. Mol. Biol. 430, 4741 (2018).CrossRefGoogle Scholar
Boeynaems, S., Alberti, S., Fawzi, N.L., Mittag, T., Polymenidou, M., Rousseau, F., Schymkowitz, J., Shorter, J., Wolozin, B., Van Den Bosch, L., Tompa, P., Fuxreiter, M., Trends Cell Biol. 28, 420 (2018).CrossRefGoogle Scholar
Alberti, S., Curr. Biol. 27, R1097 (2017).CrossRefGoogle Scholar
Spruijt, E., Sprakel, J., Cohen Stuart, M.A., van der Gucht, J., Soft Matter 6, 172 (2009).CrossRefGoogle Scholar
Hwang, D.S., Zeng, H., Srivastava, A., Krogstad, D.V., Tirrell, M., Israelachvili, J.N., Waite, J.H., Soft Matter 6, 3232 (2010).CrossRefGoogle Scholar
Kizilay, E., Kayitmazer, A.B., Dubin, P.L., Adv. Colloid Interface Sci. 167, 24 (2011).Google Scholar
Tan, Y.P., Hoon, S., Guerette, P.A., Wei, W., Hao, C., Ghadban, A., Miserez, A., Waite, J.H., Nat. Chem. Biol. 11, 488 (2015).CrossRefGoogle Scholar
Urry, D.W., J. Protein Chem. 7, 1 (1988).CrossRefGoogle Scholar
Yeo, G.C., Keeley, F.W., Weiss, A.S., Adv. Colloid Interface Sci. 167, 94 (2011).CrossRefGoogle Scholar
Wise, S.G., Yeo, G.C., Hiob, M.A., Rnjak-Kovacina, J., Kaplan, D.L., Ng, M.K.C., Weiss, A.S., Acta Biomater. 10, 1532 (2014).CrossRefGoogle Scholar
Luginbuhl, K.M., Schaal, J.L., Umstead, B., Mastria, E.M., Li, X., Banskota, S., Arnold, S., Feinglos, M., D'Alessio, D., Chilkoti, A., Nat. Biomed. Eng. 1, 0078 (2017).CrossRefGoogle Scholar
Meyer, D.E., Chilkoti, A., Nat. Biotechnol. 17, 1112 (1999).CrossRefGoogle Scholar
Roberts, S., Harmon, T.S., Schaal, J.L., Miao, V., Li, K., Hunt, A., Wen, Y., Oas, T.G., Collier, J.H., Pappu, R.V., Chilkoti, A., Nat. Mater. 17, 1154 (2018).10.1038/s41563-018-0182-6CrossRefGoogle Scholar
Brangwynne, C.P., Eckmann, C.R., Courson, D.S., Rybarska, A., Hoege, C., Gharakhani, J., Jülicher, F., Hyman, A.A., Science 324, 1729 (2009).CrossRefGoogle Scholar
Alberti, S., Gladfelter, A., Mittag, T., Cell 176, 419 (2019).CrossRefGoogle Scholar
Bracha, D., Walls, M.T., Brangwynne, C.P., Nat. Biotechnol. 37, 1435 (2019).CrossRefGoogle Scholar
Stewart, R.J., Wang, C.S., Song, I.T., Jones, J.P., Adv. Colloid Interface Sci. 239, 88 (2017).CrossRefGoogle Scholar
Stewart, R.J., Weaver, J.C., Morse, D.E., Waite, J.H., J. Exp. Biol. 207, 4727 (2004).CrossRefGoogle Scholar
Zhao, H., Sun, C., Stewart, R.J., Waite, J.H., J. Biol. Chem. 280, 42938 (2005).CrossRefGoogle Scholar
Waite, J.H., Jensen, R.A., Morse, D.E., Biochemistry 31, 5733 (1992).CrossRefGoogle Scholar
Waite, J.H., J. Exp. Biol. 220, 517 (2017).CrossRefGoogle Scholar
Wang, C.S., Stewart, R.J., Biomacromolecules 14, 1607 (2013).CrossRefGoogle Scholar
Stewart, R.J., Wang, C.S., Shao, H., Adv. Colloid Interface Sci. 167, 85 (2011).CrossRefGoogle Scholar
Winslow, B.D., Shao, H., Stewart, R.J., Tresco, P.A., Biomaterials, 31, 9373 (2010).CrossRefGoogle Scholar
Lipik, V., Zhang, L., Miserez, A., Polym. Chem. 5, 1351 (2014).CrossRefGoogle Scholar
Zhang, L., Lipik, V., Miserez, A., J. Mater. Chem. B 4, 1544 (2016).CrossRefGoogle Scholar
Lee, P.L., Messersmith, P.B., Israelachvili, J.N., Waite, J.H., Annu. Rev. Mater. Res. 41, 99 (2011).CrossRefGoogle Scholar
Harrington, M.J., Waite, J.H., J. Exp. Biol. 210, 4307 (2007).CrossRefGoogle Scholar
Guerette, P.A., Hoon, S., Seow, Y., Wong, F.T., Ho, V.H.B., Raida, M., Masic, A., Demirel, M.C., Abdon, F., Amini, S., Tay, G.Z., Ding, D., Miserez, A., Nat. Biotechnol. 31, 908 (2013).CrossRefGoogle Scholar
Gantayet, A., Rees, D.J., Sone, E.D., Mar. Biotechnol. 16, 144 (2014).CrossRefGoogle Scholar
Wei, W., Tan, Y., Rodriguez, N.R.M., Yu, J., Israelachvili, J.N., Waite, J.H., Acta Biomater. 10, 1663 (2014).CrossRefGoogle Scholar
Jehle, F., Macías-Sánchez, E., Sviben, S., Fratzl, P., Bertinetti, L., Harrington, M.J., Nat. Commun. 11, 862 (2020).CrossRefGoogle Scholar
Priemel, T., Degtyar, E., Dean, M.N., Harrington, M.J., Nat. Commun. 8, 14539 (2017).CrossRefGoogle Scholar
Harrington, M.J., Masic, A., Holten-Andersen, N., Waite, J.H., Fratzl, P., Science 328, 216 (2010).CrossRefGoogle Scholar
Miller, D.R., Das, S., Huang, K.-Y., Han, S., Israelachvili, J.N., Waite, J.H., ACS Biomater. Sci. Eng. 1, 1121 (2015).CrossRefGoogle Scholar
Hwang, D.S., Gim, Y., Yoo, H.J., Cha, H.J., Biomaterials 28, 3560 (2007).CrossRefGoogle Scholar
Lim, S., Choi, Y.S., Kang, D.G., Song, Y.H., Cha, H.J., Biomaterials 31, 3715 (2010).CrossRefGoogle Scholar
Guo, Q., Chen, J., Wang, J., Zeng, H., Yu, J., Nanoscale 12, 1307 (2020).Google Scholar
Yu, J., Wei, W., Menyo, M.S., Masic, A., Waite, J.H., Israelachvili, J.N., Biomacromolecules 14, 1072 (2013).CrossRefGoogle Scholar
Hwang, D.S., Zeng, H., Lu, Q., Israelachvili, J., Waite, J.H., Soft Matter 8, 5640 (2012).CrossRefGoogle Scholar
Lu, Q., Oh, D.X., Lee, Y., Jho, Y., Hwang, D.S., Zeng, H., Angew. Chem. Int. Ed. 52, 3944 (2013).CrossRefGoogle Scholar
Park, S., Kim, S., Jho, Y., Hwang, D.S., Langmuir 35, 16002 (2019).CrossRefGoogle Scholar
Kim, S., Huang, J., Lee, Y., Dutta, S., Yoo, H.Y., Jung, Y.M., Jho, Y., Zeng, H., Hwang, D.S., Proc. Natl. Acad. Sci. U.S.A. 113, E847 (2016).CrossRefGoogle Scholar
Seo, S., Das, S., Zalicki, P.J., Mirshafian, R., Eisenbach, C.D., Israelachvili, J.N., Waite, J.H., Ahn, B.K., J. Am. Chem. Soc. 137, 9214 (2015).CrossRefGoogle Scholar
Zhao, Q., Lee, D.W., Ahn, B.K., Seo, S., Kaufman, Y., Israelachvili, J.N., Waite, J.H., Nat. Mater. 15, 407 (2016).CrossRefGoogle Scholar
Cui, M., Wang, X., An, B., Zhang, C., Gui, X., Li, K., Li, Y., Ge, P., Zhang, J., Liu, C., Zhong, C., Sci. Adv. 5, eaax3155 (2019).Google Scholar
Israelachvili, J.N., Intermolecular and Surface Forces, 3rd ed. (Academic Press, Cambridge MA, USA, 2011).Google Scholar
Priftis, D., Farina, R., Tirrell, M., Langmuir 28, 8721 (2012).CrossRefGoogle Scholar
Clarke, M.R., Ed., A Handbook for the Identification of Cephalopod Beaks (Clarendon Press, Oxford, UK, 1986).Google Scholar
Miserez, A., Li, Y., Waite, J.H., Zok, F., Acta Biomater. 3, 139 (2007).CrossRefGoogle Scholar
Andersen, S.A., Hojrup, P., Roepstorff, P., Insect Biochem. Mol. Biol. 25, 153 (1995).CrossRefGoogle Scholar
Rubin, D., Miserez, A., Waite, J.H., in Advances in Insect Physiology, Casas, Ed., J. (Elsevier, Amsterdam, The Netherlands, 2010), vol. 38, pp. 75–133.Google Scholar
Willis, J.H., Iconomidou, V.A., Smith, V.F., Hamodrakas, S. in Comprehensive Molecular Insect Science, Gilbert, L., Iatrou, K., Gill, S., Eds. (Elsevier, Oxford, UK, 2005), vol. 4, pp. 79–110.CrossRefGoogle Scholar
Miserez, A., Schneberk, T., Sun, C., Zok, F. W., Waite, J.H., Science 319, 1816 (2008).CrossRefGoogle Scholar
Miserez, A., Rubin, D., Waite, J.H., J. Biol. Chem. 285, 38115 (2010).CrossRefGoogle Scholar
Schaefer, J., Kramer, K., Garbow, J., Jacob, G., Stejskal, E., Hopkins, T., Speirs, R., Science 235, 1200 (1987).10.1126/science.3823880CrossRefGoogle Scholar
Andersen, S.A., Insect Biochem. Mol. Biol. 40, 166 (2010).CrossRefGoogle Scholar
Ozsolak, F., Milos, P.M., Nat. Rev. Genet. 12, 87 (2011).CrossRefGoogle Scholar
Grabherr, M.G., Haas, B.J., Yassour, M., Levin, J.Z., Thompson, D.A., Amit, I., Adiconis, X., Fan, L., Raychowdhury, R., Zeng, Q., Chen, Z., Mauceli, E., Hacohen, N., Gnirke, A., Rhind, N., Di Palma, F., Birren, B.W., Nusbaum, C., Lindblad-Toh, K., Friedman, N., Regev, A., Nat. Biotechnol. 29, 644 (2011).CrossRefGoogle Scholar
Dilly, P.N., Nixon, M., Cell Tissue Res. 167, 229 (1976).CrossRefGoogle Scholar
Ma, B., Zhang, K., Hendrie, C., Liang, C., Li, M., Doherty-Kirby, A., Lajoie, G., Rapid Commun. Mass Spectrom. 17, 2337 (2003).CrossRefGoogle Scholar
Guerette, P.A., Hoon, S., Ding, D., Amini, S., Masic, A., Venkatesh, B., Ravi, V., Weaver, J.C., Miserez, A., ACS Nano 8, 7170 (2014).CrossRefGoogle Scholar
Loke, J.J., Kumar, A., Hoon, S., Verma, C., Miserez, A., Biomacromolecules 18, 931 (2017).CrossRefGoogle Scholar
Amini, S., Tadayon, M., Loke, J.J., Kumar, A., Kanagavel, D., Le Ferrand, H., Duchamp, M., Raida, M., Sobota, R.M., Chen, L., Hoon, S., Miserez, A., Proc. Natl. Acad. Sci. U.S.A. 116, 8685 (2019).CrossRefGoogle Scholar
Ping, Y., Ding, D., Ramos, R.A.N.S., Mohanram, H., Deepankumar, K., Gao, J., Tang, G., Miserez, A., ACS Nano 11, 4528 (2017).CrossRefGoogle Scholar
Hiew, S.H., Miserez, A., ACS Biomater. Sci. Eng. 3, 680 (2017).Google Scholar
Ding, D., Pan, J., Lim, S.H., Amini, S., Kang, L., Miserez, A., J. Mater. Chem. B 5, 8467 (2017).CrossRefGoogle Scholar
Deepankumar, K., Lim, C., Polte, I., Zappone, B., Labate, C., De Santo, M.P., Mohanram, H., Palaniappan, A., Hwang, D.S., Miserez, A., Adv. Funct. Mater. 30, 1907534 (2020).CrossRefGoogle Scholar
Cai, H., Gabryelczyk, B., Manimekalai, M.S.S., Grüber, G., Salentinig, S., Miserez, A., Soft Matter 13, 7740 (2017).CrossRefGoogle Scholar
Gabryelczyk, B., Cai, H., Shi, X., Yue, S., Swinkels, P.J.M., Salentinig, S., Pervushin, K., Miserez, A., Nat. Commun. 10, 5465 (2019).CrossRefGoogle Scholar
Uversky, V.N., Adv. Colloid Interface Sci. 239, 97 (2017).CrossRefGoogle Scholar
Brady, J.P., Farber, P.J., Sekhar, A., Lin, Y.-H., Huang, R., Bah, A., Nott, T.J., Chan, H.S., Baldwin, A.J., Forman-Kay, J.D., Kay, L.E., Proc. Natl. Acad. Sci. U.S.A. 114, E8194 (2017).CrossRefGoogle Scholar
Reichheld, S.E., Muiznieks, L.D., Keeley, F.W., Sharpe, S., Proc. Natl. Acad. Sci. U.S.A. 114, E4408 (2017).CrossRefGoogle Scholar
Murray, D.T., Kato, M., Lin, Y., Thurber, K.R., Hung, I., McKnight, S.L., Tycko, R., Cell 171, 615 (2017).CrossRefGoogle Scholar
Lampel, A., Chem 6, 1222 (2020).CrossRefGoogle Scholar
De Yoreo, J.J., Sommerdijk, N.A.J.M., Nat. Rev. Mater. 1, 16035 (2016).CrossRefGoogle Scholar
Le Ferrand, H., Duchamp, M., Gabryelczyk, B., Cai, H., Miserez, A., J. Am. Chem. Soc. 141, 7202 (2019).CrossRefGoogle Scholar
Black, K.A., Priftis, D., Perry, S.L., Yip, J., Byun, W.Y., Tirrell, M., ACS Macro Lett. 3, 1088 (2014).CrossRefGoogle Scholar
Johnson, N.R., Kruger, M., Goetsch, K.P., Zilla, P., Bezuidenhout, D., Wang, Y., Davies, N.H., ACS Biomater. Sci. Eng. 1, 753 (2015).CrossRefGoogle Scholar
Lim, Z.W., Ping, Y., Miserez, A., Bioconjug. Chem. 29, 2176 (2018).CrossRefGoogle Scholar
Priftis, D., Leon, L., Song, Z., Perry, S.L., Margossian, K.O., Tropnikova, A., Cheng, J., Tirrell, M., Angew. Chem. Int. Ed. 54, 11128 (2015).Google Scholar
Lim, Z.W., Varma, V., Ramanujan, R.V., Miserez, A., Acta Biomater. 110, 221 (2020).CrossRefGoogle Scholar
Du, S., Liew, S.S., Li, L., Yao, S.Q., J. Am. Chem. Soc. 140, 15986 (2018).CrossRefGoogle Scholar
Xia, X.X., Qian, Z.G., Ki, C.S., Park, Y.H., Kaplan, D.L., Lee, S.Y., Proc. Natl. Acad. Sci. U.S.A. 107, 14059 (2010).CrossRefGoogle Scholar
Andersson, M., Jia, Q., Abella, A., Lee, X.-Y., Landreh, M., Purhonen, P., Hebert, H., Tenje, M., Robinson, C.V., Meng, Q., Plaza, G.R., Johansson, J., Rising, A., Nat. Chem. Biol. 13, 262 (2017).CrossRefGoogle Scholar
Mohammadi, P., Aranko, A.S., Lemetti, L., Cenev, Z., Zhou, Q., Virtanen, S., Landowski, C.P., Penttilä, M., Fischer, W.J., Wagermaier, W., Linder, M.B., Commun. Biol. 1, 86 (2018).CrossRefGoogle Scholar
Mohammadi, P., Beaune, G., Stokke, B.T., Timonen, J.V.I., Linder, M.B., ACS Macro Lett. 7, 1120 (2018).CrossRefGoogle Scholar
Mohammadi, P., Aranko, A.S., Landowski, C.P., Ikkala, O., Jaudzems, K., Wagermaier, W., Linder, M.B., Sci. Adv. 5, eaaw2541 (2019).CrossRefGoogle Scholar
Geyer, R., Jambeck, J.R., Law, K.L., Sci. Adv. 3, e1700782 (2017).CrossRefGoogle Scholar