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Soft matter and nanomaterials characterization by cryogenic transmission electron microscopy

  • John Watt (a1), Dale L. Huber (a2) and Phoebe L. Stewart (a3)


Soft matter has historically been an unlikely candidate for investigation by electron microscopy techniques due to damage by the electron beam as well as inherent instability under a high vacuum environment. Characterization of soft matter has often relied on ensemble-scattering techniques. The recent development of cryogenic transmission electron microscopy (cryo-TEM) provides the soft matter community with an exciting opportunity to probe the structure of soft materials in real space. Cryo-TEM reduces beam damage and allows for characterization in a native, frozen-hydrated state, providing direct visual representation of soft structure. This article reviews cryo-TEM in soft materials characterization and illustrates how it has provided unique insights not possible by traditional ensemble techniques. Soft matter systems that have benefited from the use of cryo-TEM include biological-based “soft” nanoparticles (e.g., viruses and conjugates), synthetic polymers, supramolecular materials as well as the organic–inorganic interface of colloidal nanoparticles. Many challenges remain, such as combining structural and chemical analyses; however, the opportunity for soft matter research to leverage newly developed cryo-TEM techniques continues to excite.



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1.Cheng, Y.F., Science 361, 876 (2018).
2.Danev, R., Yanagisawa, H., Kikkawa, M., Trends Biochem. Sci. 44, 837 (2019).
3.Kuhlbrandt, W., Science 343, 1443 (2014).
4.Nogales, E., Scheres, S.H., Mol. Cell 58, 677 (2015).
5.Beck, M., Baumeister, W., Trends Cell Biol . 26, 825 (2016).
6.Koning, R.I., Koster, A.J., Sharp, T.H., Ann. Anat. 217, 82 (2018).
7.Weber, M.S., Wojtynek, M., Medalia, O., Cells 8, 57 (2019).
8.Veliz, F.A., Ma, Y.F., Molugu, S.K., Tiu, B.D.B., Stewart, P.L., French, R.H., Steinmetz, N.F., Adv. Biosyst. 1, 1700088 (2017).
9.McKenzie, B.E., de Visser, J.F., Portale, G., Hermida-Merino, D., Friedrich, H., Bomans, P.H.H., Bras, W., Monaghan, O.R., Holder, S.J., Sommerdijk, N.A.J.M., Soft Matter 12, 4113 (2016).
10.Hernandez, C., Gulati, S., Fioravanti, G., Stewart, P.L., Exner, A.A., Sci. Rep. 7, 13517 (2017).
11.Stewart, P.L., Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 9, e1417 (2017).
12.Jiang, W., Tang, L., Curr. Opin. Struct. Biol. 46, 122 (2017).
13.Lee, P.W., Isarov, S.A., Wallat, J.D., Molugu, S.K., Shukla, S., Sun, J.E., Zhang, J., Zheng, Y., Lucius Dougherty, M., Konkolewicz, D., Stewart, P.L., Steinmetz, N.F., Hore, M.J., Pokorski, J.K., J. Am. Chem. Soc. 139, 3312 (2017).
14.Jun, H., Shepherd, T.R., Zhang, K., Bricker, W.P., Li, S., Chiu, W., Bathe, M., ACS Nano 13, 2083 (2019).
15.Gulati, N.M., Pitek, A.S., Steinmetz, N.F., Stewart, P.L., Nanoscale 9, 3408 (2017).
16.Demurtas, D., Guichard, P., Martiel, I., Mezzenga, R., Hebert, C., Sagalowicz, L., Nat. Commun. 6, 8915 (2015).
17.Vanzo, E., J. Polym. Sci. A Polym. Chem. 4, 1727 (1966).
18.Kinning, D.J., Winey, K.I., Thomas, E.L., Macromolecules 21, 3502 (1988).
19.Thomas, E.L., Anderson, D.M., Henkee, C.S., Hoffman, D., Nature 334, 598 (1988).
20.Vinson, P.K., Bellare, J.R., Davis, H.T., Miller, W.G., Scriven, L.E., J. Colloid Interface Sci. 142, 74 (1991).
21.Lobling, T.I., Haataja, J.S., Synatschke, C.V., Schacher, F.H., Muller, M., Hanisch, A., Groschel, A.H., Muller, A.H., ACS Nano 8, 11330 (2014).
22.Sehgal, A., Seery, T.A.P., Macromolecules 32, 7807 (1999).
23.Wirix, M.J., Bomans, P.H., Friedrich, H., Sommerdijk, N.A., de With, G., Nano Lett . 14, 2033 (2014).
24.Magdassi, S., Grouchko, M., Toker, D., Kamyshny, A., Balberg, I., Millo, O., Langmuir 21, 10264 (2005).
25.Monson, T.C., Venturini, E.L., Petkov, V., Ren, Y., Lavin, J.M., Huber, D.L., J. Magn. Magn. Mater. 331, 156 (2013).
26.Bishop, K.J.M., Wilmer, C.E., Soh, S., Grzybowski, B.A., Small 5, 1600 (2009).
27.Sabyrov, K., Burrows, N.D., Penn, R.L., Chem. Mater. 25, 1408 (2013).
28.Kirillova, A., Schliebe, C., Stoychev, G., Jakob, A., Lang, H., Synytska, A., ACS Appl. Mater. Interfaces 7, 21218 (2015).
29.Ilett, M., Brydson, R., Brown, A., Hondow, N., Micron 120, 35 (2019).
30.Mousseau, F., Oikonomou, E.K., Baldim, V., Mornet, S., Berret, J.F., Colloids Interfaces 2, 50 (2018).
31.Wang, F., Zhang, X., Liu, Y., Lin, Z.Y., Liu, B., Liu, J., Angew. Chem. Int. Ed. Engl. 55, 12063 (2016).
32.Liu, X.R., Li, X.Q., Xu, W., Zhang, X.H., Huang, Z.C., Wang, F., Liu, J.W., Langmuir 34, 6628 (2018).
33.Zivanovic, V., Kochovski, Z., Arenz, C., Lu, Y., Kneipp, J., J. Phys. Chem. Lett. 9, 6767 (2018).
34.Qiao, X.G., Lambert, O., Taveau, J.C., Dugas, P.Y., Charleux, B., Lansalot, M., Bourgeat-Lami, E., Macromolecules 50, 3796 (2017).
35.Burrows, N.D., Penn, R.L., Microsc. Microanal. 19, 1542 (2013).
36.Miao, J., Ercius, P., Billinge, S.J.L., Science 353, aaf2157 (2016).
37.Zachman, M.J., Tu, Z., Choudhury, S., Archer, L.A., Kourkoutis, L.F., Nature 560, 345 (2018).
38.Simocko, C.K., Frischknecht, A.L., Huber, D.L., ACS Macro Lett. 5, 149 (2016).

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Soft matter and nanomaterials characterization by cryogenic transmission electron microscopy

  • John Watt (a1), Dale L. Huber (a2) and Phoebe L. Stewart (a3)


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