Statistical mechanics of biomolecular condensates via cavity methods
Nino Lauber,
Ondrej Tichacek,
Rudrarup Bose,
Christoph Flamm,
Luca Leuzzi,
T-Y Dora Tang,
Kepa Ruiz-Mirazo,
Daniele De Martino
Affiliations
Nino Lauber
Biofisika Institute (CSIC, UPV/EHU), Barrio Sarriena s/n. 48940 Leioa, Bizkaia, Spain; Donostia International Physics Center (DIPC), Paseo Manuel de Lardizabal, 4, 20018 Donostia-San Sebastian, Gipuzkoa, Spain; Department of Philosophy (UPV/EHU), Avenida de Tolosa 70, 20018 Donostia–San Sebastian, Gipuzkoa, Spain
Ondrej Tichacek
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, 160 00 Praha 6, Czech Republic
Rudrarup Bose
Max Planck Institute of Molecular Cell Biology & Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany
Christoph Flamm
Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria
Luca Leuzzi
Department of Physics, Universitá di Roma la Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy; Institute of Nanotechnology, Soft and Living Matter Laboratory, Consiglio Nazionale delle Ricerche (CNR-NANOTEC), Piazzale Aldo Moro 5, 00185 Rome, Italy
T-Y Dora Tang
Max Planck Institute of Molecular Cell Biology & Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany
Kepa Ruiz-Mirazo
Biofisika Institute (CSIC, UPV/EHU), Barrio Sarriena s/n. 48940 Leioa, Bizkaia, Spain; Department of Philosophy (UPV/EHU), Avenida de Tolosa 70, 20018 Donostia–San Sebastian, Gipuzkoa, Spain
Daniele De Martino
Biofisika Institute (CSIC, UPV/EHU), Barrio Sarriena s/n. 48940 Leioa, Bizkaia, Spain; Ikerbasque Foundation, Alameda Urquijo, 36, 48011 Bilbao, Bizkaia, Spain; Corresponding author
Summary: Physical mechanisms of phase separation in living systems play key physiological roles and have recently been the focus of intensive studies. The strongly heterogeneous nature of such phenomena poses difficult modeling challenges that require going beyond mean-field approaches based on postulating a free energy landscape. The pathway we take here is to calculate the partition function starting from microscopic interactions by means of cavity methods, based on a tree approximation for the interaction graph. We illustrate them on the binary case and then apply them successfully to ternary systems, in which simpler one-factor approximations are proved inadequate. We demonstrate the agreement with lattice simulations and contrast our theory with coacervation experiments of associative de-mixing of nucleotides and poly-lysine. Different types of evidence are provided to support cavity methods as ideal tools for modeling biomolecular condensation, giving an optimal balance between the consideration of spatial aspects and fast computational results.