Our work on intracellular organization spans biology, engineering, and physics, and we believe that thes efforts have the potential to uncover entirely new physics. For example, although our work has revealed that the thermodynamic concept of liquid-liquid phase equilibrium is useful for understanding the cytoplasm/nucleoplasm, living cells are out-of-equilibrium systems. One primary manifestations of this nonequilibrium behavior is the ATP hydrolysis which occurs throughout the cell, associated with activity of a plethora of ATP-dependent enzymes (molecular motors, helicase etc.) – see e.g. Brangwynne JCB 2008, Brangwynne et.al. PNAS 2011, Feric et.al. Cell 2016. A second related manifestation of intracellular nonequilibrium is post-translational protein modifications (PTMs), such as phosphorylation of particular IDR residues, which tune the intermolecular interactions underlying phase behavior (for a review, see Brangwynne et.al. Nature Physics 2015). Thus, the phase diagrams that we have been able to map in living cells (e.g. Bracha et.al. Cell 2018) may ultimately reflect and underlying non-equilibrium state. How this nonequilibrium behavior impacts classical features of phase behavior, such as nucleation and growth, spinodal decomposition, and criticality, and its dependence on IDR sequence, remain poorly understood and of great interest to us. Some of this work is being pursued together with our theory/computation collaborators, including Mikko Haataja (Princeton Mechanical & Aerospace Engineering), Ned Wingreen (Princeton Molecular Biology), Rohit Pappu (Washington University in St. Louis), and Thanos Panagiatopoulos (Princeton Chemical & Biological Engineering).
Figure - Intracellular phase diagram. We have begun mapping the first intracellular phase diagrams, utilizing the biomimetic Corelet system (Bracha et.al. Cell 2018). This phase diagram describes the behavior of the oligomerized FUS IDR, and shows features comparable to those well-known in non-living systems.