Abstract
For effective of orchestration of biochemical reactions that are optimized in different physicochemical environments, cells are evolved to carry various non-membranous biomolecular condensates in addition to conventional membrane-bound organelles. Recent studies have revealed that these biomolecular condensates are made up of proteins and RNAs of a specific character and are formed via liquid–liquid phase separation. Here, we review recent theoretical attempts trying to understand the biophysical principles underlying the formation and regulation of these intriguing structures. Comprehension of the biophysical underpinnings regarding the occurrence and the behavior of biomolecular condensates will make deeper insights into their biological functions possible.
Similar content being viewed by others
References
J.A. Riback, C.D. Katanski, J.L. Kear-Scott, E.V. Pilipenko, A.E. Rojek, T.R. Sosnick, D.A. Drummond, Cell 168, 1028 (2017)
C. Iserman, C. Desroches Altamirano, C. Jegers, U. Friedrich, T. Zarin, A.W. Fritsch, M. Mittasch, A. Domingues, L. Hersemann, M. Jahnel, D. Richter, U.-P. Guenther, M.W. Hentze, A.M. Moses, A.A. Hyman, G. Kramer, M. Kreysing, T.M. Franzmann, S. Alberti, Cell 181, 818 (2020)
J. Guillén-Boixet, A. Kopach, A.S. Holehouse, S. Wittmann, M. Jahnel, R. Schlüßler, K. Kim, I.R.E.A. Trussina, J. Wang, D. Mateju, I. Poser, S. Maharana, M. Ruer-Gruß, D. Richter, X. Zhang, Y.T. Chang, J. Guck, A. Honigmann, J. Mahamid, A.A. Hyman, R.V. Pappu, S. Alberti, T.M. Franzmann, Cell 181, 346 (2020)
P. Yang, C. Mathieu, R.M. Kolaitis, P. Zhang, J. Messing, U. Yurtsever, Z. Yang, J. Wu, Y. Li, Q. Pan, J. Yu, E.W. Martin, T. Mittag, H.J. Kim, J.P. Taylor, Cell 181, 325 (2020)
F. Wippich, B. Bodenmiller, M.G. Trajkovska, S. Wanka, R. Aebersold, L. Pelkmans, Cell 152, 791 (2013)
J. Ayache, M. Bénard, M. Ernoult-Lange, N. Minshall, N. Standart, M. Kress, D. Weil, Mol. Biol. Cell 26, 2579 (2015)
B.S. Rao, R. Parker, Proc. Natl. Acad. Sci. U.S.A. 114, E9569 (2017)
S.A. Fromm, J. Kamenz, E.R. Nöldeke, A. Neu, G. Zocher, R. Sprangers, Angew. Chemie Int. Ed. 53, 7354 (2014)
L. Latonen, Front. Cell. Neurosci. 13, 1 (2019)
C.P. Brangwynne, T.J. Mitchison, A.A. Hyman, Proc. Natl. Acad. Sci. U.S.A. 108, 4334 (2011)
K.E. Handwerger, J.A. Cordero, J.G. Gall, Mol. Biol. Cell 16, 202 (2005)
S. Contreras-Martos, A. Piai, S. Kosol, M. Varadi, A. Bekesi, P. Lebrun, A.N. Volkov, K. Gevaert, R. Pierattelli, I.C. Felli, P. Tompa, Sci. Rep. 7, 1 (2017)
F.M. Boisvert, M.J. Kruhlak, A.K. Box, M.J. Hendzel, D.P. Bazett-Jones, J. Cell Biol. 152, 1099 (2001)
S. Weidtkamp-Peters, T. Lenser, D. Negorev, N. Gerstner, T.G. Hofmann, G. Schwanitz, C. Hoischen, G. Maul, P. Dittrich, P. Hemmerich, J. Cell Sci. 121, 2731 (2008)
L. Galganski, M.O. Urbanek, W.J. Krzyzosiak, Nucleic Acids Res. 45, 10350 (2017)
Y. Lu, T. Wu, O. Gutman, H. Lu, Q. Zhou, Y.I. Henis, K. Luo, Nat. Cell Biol. 22, 453 (2020)
B.R. Sabari, A. Dall’Agnese, A. Boija, I.A. Klein, E.L. Coffey, K. Shrinivas, B.J. Abraham, N.M. Hannett, A.V. Zamudio, J.C. Manteiga, C.H. Li, Y.E. Guo, D.S. Day, J. Schuijers, E. Vasile, S. Malik, D. Hnisz, T.I. Lee, I.I. Cisse, R.G. Roeder, P.A. Sharp, A.K. Chakraborty, R.A. Young, Science 361, 379 (2018)
S. Elbaum-Garfinkle, Y. Kim, K. Szczepaniak, C.C.H. Chen, C.R. Eckmann, S. Myong, C.P. Brangwynne, Proc. Natl. Acad. Sci. U.S.A. 112, 7189 (2015)
C.P. Brangwynne, C.R. Eckmann, D.S. Courson, A. Rybarska, C. Hoege, J. Gharakhani, F. Jülicher, A.A. Hyman, Science 324, 1729 (2009)
S. Boeynaems, S. Alberti, N.L. Fawzi, T. Mittag, M. Polymenidou, F. Rousseau, J. Schymkowitz, J. Shorter, B. Wolozin, L. Van Den Bosch, P. Tompa, M. Fuxreiter, Trends Cell Biol. 28, 420 (2018)
S.F. Banani, H.O. Lee, A.A. Hyman, M.K. Rosen, Nat. Rev. Mol. Cell Biol. 18, 285 (2017)
S. Banjade, M.K. Rosen, Elife 3, e04123 (2014)
T.S. Harmon, A.S. Holehouse, M.K. Rosen, R.V. Pappu, Elife 6, 1 (2017)
A.E. Posey, A.S. Holehouse, R.V. Pappu, in Phase Separation of Intrinsically Disordered Proteins, Methods in Enzymology (Elsevier, 2018), vol. 611, pp. 1–30
A.A. Hyman, C.A. Weber, F. Jülicher, Annu. Rev. Cell Dev. Biol. 30, 39 (2014)
C.P. Brangwynne, Soft Matter 7, 3052 (2011)
C.F. Lee, C.P. Brangwynne, J. Gharakhani, A.A. Hyman, F. Jülicher, Phys. Rev. Lett. 111, 1 (2013)
C.J. Oldfield, A.K. Dunker, Annu. Rev. Biochem. 83, 553 (2014)
C.P. Brangwynne, P. Tompa, R.V. Pappu, Nat. Phys. 11, 899 (2015)
J.T.G. Overbeek, M.J. Voorn, J. Cell. Comp. Physiol. 49, 7 (1957)
R.W. Style, T. Sai, N. Fanelli, M. Ijavi, K. Smith-Mannschott, Q. Xu, L.A. Wilen, E.R. Dufresne, Phys. Rev. X 8, 11028 (2018)
K.A. Rosowski, T. Sai, E. Vidal-Henriquez, D. Zwicker, R.W. Style, E.R. Dufresne, Nat. Phys. 16, 422 (2020)
A. Molliex, J. Temirov, J. Lee, M. Coughlin, A.P. Kanagaraj, H.J. Kim, T. Mittag, J.P. Taylor, Cell 163, 123 (2015)
M. Zeng, Y. Shang, Y. Araki, T. Guo, R.L. Huganir, M. Zhang, Cell 166, 1163 (2016)
X. Su, J.A. Ditlev, E. Hui, W. Xing, S. Banjade, J. Okrut, D.S. King, J. Taunton, M.K. Rosen, R.D. Vale, Science 352, 595 (2016)
Y.I. Henis, B. Rotblat, Y. Kloog, Methods 40, 183 (2006)
T.P. Dao, R.M. Kolaitis, H.J. Kim, K. O’Donovan, B. Martyniak, E. Colicino, H. Hehnly, J.P. Taylor, C.A. Castañeda, Mol. Cell 69, 965 (2018)
N.O. Taylor, M.T. Wei, H.A. Stone, C.P. Brangwynne, Biophys. J. 117, 1285 (2019)
Z. Wang, G. Zhang, H. Zhang, Biophys. Rep. 5, 1 (2019)
G. Zhang, Z. Wang, Z. Du, H. Zhang, Cell 174, 1492 (2018)
D.M. Mitrea, J.A. Cika, C.B. Stanley, A. Nourse, P.L. Onuchic, P.R. Banerjee, A.H. Phillips, C.G. Park, A.A. Deniz, R.W. Kriwacki, Nat. Commun. 9, 1 (2018)
Z. Monahan, V.H. Ryan, A.M. Janke, K.A. Burke, S.N. Rhoads, G.H. Zerze, R. O’Meally, G.L. Dignon, A.E. Conicella, W. Zheng, R.B. Best, R.N. Cole, J. Mittal, F. Shewmaker, N.L. Fawzi, EMBO J. 36, 2951 (2017)
J. Wang, J.M. Choi, A.S. Holehouse, H.O. Lee, X. Zhang, M. Jahnel, S. Maharana, R. Lemaitre, A. Pozniakovsky, D. Drechsel, I. Poser, R.V. Pappu, S. Alberti, A.A. Hyman, Cell 174, 688 (2018)
V.N. Uversky, I.M. Kuznetsova, K.K. Turoverov, B. Zaslavsky, FEBS Lett. 589, 15 (2015)
D.W. Sanders, N. Kedersha, D.S.W. Lee, A.R. Strom, V. Drake, J.A. Riback, D. Bracha, J.M. Eeftens, A. Iwanicki, A. Wang, M.T. Wei, G. Whitney, S.M. Lyons, P. Anderson, W.M. Jacobs, P. Ivanov, C.P. Brangwynne, Cell 181, 306 (2020)
T.J. Nott, E. Petsalaki, P. Farber, D. Jervis, E. Fussner, A. Plochowietz, T.D. Craggs, D.P. Bazett-Jones, T. Pawson, J.D. Forman-Kay, A.J. Baldwin, Mol. Cell 57, 936 (2015)
T. Yamazaki, S. Souquere, T. Chujo, S. Kobelke, Y.S. Chong, A.H. Fox, C.S. Bond, S. Nakagawa, G. Pierron, T. Hirose, Mol. Cell 70, 1038 (2018)
Y. Zhang, M. Yang, S. Duncan, X. Yang, M.A.S. Abdelhamid, L. Huang, H. Zhang, P.N. Benfey, Z.A.E. Waller, Y. Ding, Nucleic Acids Res. 47, 11746 (2019)
A. Patel, L. Malinovska, S. Saha, J. Wang, S. Alberti, Y. Krishnan, A.A. Hyman, Science 356, 753 (2017)
A. Soranno, I. Koenig, M.B. Borgia, H. Hofmann, F. Zosel, D. Nettels, B. Schuler, Proc. Natl. Acad. Sci. U.S.A. 111, 4874 (2014)
Y. Shin, C.P. Brangwynne, Science 357, 1253 (2017)
A. Khong, T. Matheny, S. Jain, S.F. Mitchell, J.R. Wheeler, R. Parker, Mol. Cell 68, 808 (2017)
S.C. Bunnell, D.I. Hong, J.R. Kardon, T. Yamazaki, C.J. McGlade, V.A. Barr, L.E. Samelson, J. Cell Biol. 158, 1263 (2002)
P.J. Flory, J. Chem. Phys. 10, 51 (1942)
R.K. Das, K.M. Ruff, R.V. Pappu, Curr. Opin. Struct. Biol. 32, 102 (2015)
Y. Shin, Y.C. Chang, D.S.W. Lee, J. Berry, D.W. Sanders, P. Ronceray, N.S. Wingreen, M. Haataja, C.P. Brangwynne, Cell 175, 1481 (2018)
F.F. Abraham, Homogeneous Nucleation Theory (Elsevier, Academic Press, New York, 1974).
Acknowledgements
This work was supported by the National Research Foundation of Korea (2018R1C1B5045902 and 2019R1F1A1057948), the DGIST R&D Program of the Ministry of Science and ICT of Korea (20-CoE-BT-04) and in part by the start-up funds from Daegu Gyeongbuk Institute of Science & Technology (DGIST) to J.-C.L.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kim, J., Gwak, E. & Lee, JC. Biophysical underpinnings regarding the formation and the regulation of biomolecular condensates. J. Korean Phys. Soc. 78, 393–400 (2021). https://doi.org/10.1007/s40042-021-00073-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40042-021-00073-7