Alexander Yu. Grosberg

Biomolecular condensates govern essential cellular processes yet elude description by traditional equilibrium models. This roadmap, distilled from structured discussions at a workshop and reflecting the consensus of its participants, clarifies key concepts for researchers, funding bodies, and journals. After unifying terminology that often separates disciplines, we outline the core physics of condensate formation, review their biological roles, and identify outstanding challenges in nonequilibrium theory, multiscale simulation, and quantitative in-cell measurements. We close with a forward-looking outlook to guide coordinated efforts toward predictive, experimentally anchored understanding and control of biomolecular condensates.

Motivated by questions in biological physics, we consider a model in which different Brownian particles interact with different thermostats. Computer simulations show that hot particles (i.e., interacting with the hot bath) attract each other when placed in an environment of colder particles (i.e., interacting with the cold thermostat). This paper presents a simple calculation that sheds light on the physical nature of this attraction.

We solve a hydrodynamic model of active chromatin dynamics, within a confined geometry simulating the cell nucleus. Using both analytical and numerical met

We discover a new type of nonequilibrium phase transition in a model of chromatin dynamics, which accounts for the coherent motions that have been observed in experiment. The coherent motion is due to the long-range cooperation of molecular motors tethered to chromatin. Cooperation occurs if each motor acts simultaneously on the polymer and the surrounding solvent, exerting on them equal and opposite forces. This drives the flow of solvent past the polymer, which in turn affects the orientation of nearby motors and, if the drive is strong enough, an active polar (“ferromagnetic”) phase of motors can spontaneously form. Depending on boundary conditions, either transverse flows or sustained longitudinal oscillations and waves are possible. Predicted length scales are consistent with experiments. We now have in hand a coarse-grained description of chromatin dynamics which reproduces the directed coherent flows of chromatin seen in experiments. This field-theoretic description can be analytically coupled to other features of the nuclear environment such as fluctuating or porous boundaries, local heterogeneities in the distribution of chromatin or its activity, leading to insights on the effects of activity on the cell nucleus and its contents.

We discover a new type of nonequilibrium phase transition in a model of chromatin dynamics, which accounts for the coherent motions that have been observed in experiment. The coherent motion is due to the long-range cooperation of molecular motors tethered to chromatin. Cooperation occurs if each motor acts simultaneously on the polymer and the surrounding solvent, exerting on them equal and opposite forces. This drives the flow of solvent past the polymer, which in turn affects the orientation of nearby motors and, if the drive is strong enough, an active polar (``ferromagnetic'') phase of motors can spontaneously form. Depending on boundary conditions, either transverse flows, or sustained longitudinal oscillations and waves are possible. Predicted time and length scales are consistent with experiments. We now have in hand a coarse-grained description of chromatin dynamics which reproduces the directed coherent flows of chromatin seen in experiments. This field-theoretic description can be analytically coupled to other features of the nuclear environment such as fluctuating or porous boundaries, local heterogeneities in the distribution of chromatin or its activity, leading to insights on the effects of activity on the cell nucleus and its contents.

We solve a hydrodynamic model of active chromatin dynamics, within a confined geometry simulating the cell nucleus. Using both analytical and numerical methods, we describe the behavior of the chromatin polymer driven by the activity of motors having polar symmetry, both in the linear response regime as well as in the long-term, fully nonlinear regime of the flows. The introduction of a boundary induces a particular geometry in the flows of chromatin, which we describe using vector spherical harmonics, a tool which greatly simplifies both our analytical and numerical approaches. We find that the long-term behavior of this model in confinement is dominated by steady, transverse flows of chromatin which circulate around the spherical domain. These circulating flows are found to be robust to perturbations, and their characteristic size is set by the size of the domain. This gives us further insight into active chromatin dynamics in the cell nucleus, and provides a foundation for development of further, more complex models of active chromatin dynamics.

We classify active processes driving dynamics in the cell nucleus based on their symmetry and examine their effect on both chromatin and nucleoplasmic flows.