TY - JOUR
T1 - Single-Protein Collapse Determines Phase Equilibria of a Biological Condensate
AU - Chou, Han Yi
AU - Aksimentiev, Aleksei
N1 - This work was supported via grants from the National Science Foundation (PHY-1430124, DMR-1827346) and the National Institutes of Health (P41-GM104601). Computer time was provided by the Leadership Resource Allocation MCB20012 on Frontera at Texas Advanced Computing Center. We are grateful to Dr. Xiangze Zeng from the Pappu lab at Washington University in St. Louis for sharing unpublished results with us, guiding us through our usage of the theory of Raos and Allegra, and for fostering transparency in scientific communication.
PY - 2020/6/18
Y1 - 2020/6/18
N2 - Recent advances in microscopy of living cells have established membraneless organelles as critical elements of diverse biological processes. The body of experimental work suggests that formation of such organelles is driven by liquid-liquid phase separation, a physical process that has been studied extensively for both simple liquids and mixtures of polymers. Here, we combine molecular dynamics simulations with polymer theory to show that the thermodynamic behavior of one particular biomolecular condensate - fused in sarcoma (FUS) - can be quantitatively accounted for at the level of the chain collapse theory. First, we show that a particle-based molecular dynamics model can reproduce known phase separation properties of a FUS condensate, including its critical concentration and susceptibility to mutations. Next, we obtain a polymer physics representation of a FUS condensate by examining the behavior of a single FUS protein as a function of temperature. We use the chain collapse theory to determine the thermodynamic properties of the condensate and to characterize changes in the single-chain conformation at the onset of phase separation. Altogether, our findings suggest that the phase behavior of FUS condensates can be explained by the properties of individual FUS proteins and that the change in the FUS conformation is the main force driving for the phase separation.
AB - Recent advances in microscopy of living cells have established membraneless organelles as critical elements of diverse biological processes. The body of experimental work suggests that formation of such organelles is driven by liquid-liquid phase separation, a physical process that has been studied extensively for both simple liquids and mixtures of polymers. Here, we combine molecular dynamics simulations with polymer theory to show that the thermodynamic behavior of one particular biomolecular condensate - fused in sarcoma (FUS) - can be quantitatively accounted for at the level of the chain collapse theory. First, we show that a particle-based molecular dynamics model can reproduce known phase separation properties of a FUS condensate, including its critical concentration and susceptibility to mutations. Next, we obtain a polymer physics representation of a FUS condensate by examining the behavior of a single FUS protein as a function of temperature. We use the chain collapse theory to determine the thermodynamic properties of the condensate and to characterize changes in the single-chain conformation at the onset of phase separation. Altogether, our findings suggest that the phase behavior of FUS condensates can be explained by the properties of individual FUS proteins and that the change in the FUS conformation is the main force driving for the phase separation.
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U2 - 10.1021/acs.jpclett.0c01222
DO - 10.1021/acs.jpclett.0c01222
M3 - Article
C2 - 32426986
AN - SCOPUS:85086749194
SN - 1948-7185
VL - 11
SP - 4923
EP - 4929
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 12
ER -