Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userBridging-induced microphase separation: photobleaching experiments, chromatin domains, and the need for active reactions
75
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
We review the mechanism and consequences of the bridging-induced attraction, a generic biophysical principle which underpins some existing models for chromosome organisation in 3-D. This attraction, which was revealed in polymer physics-inspired computer simulations, is a generic clustering tendency arising in multivalent chromatin-binding proteins, and it provides an explanation for the biogenesis of nuclear bodies and transcription factories via microphase separation. Including post-translational modification reactions involving these multivalent proteins can account for the fast dynamics of the ensuing clusters, as is observed via microscopy and photobleaching experiments. The clusters found in simulations also give rise to chromatin domains which conform well with the observation of A/B compartments in HiC experiments.
rate research
Read More
We perform simulations of a system containing simple model proteins and a polymer representing chromatin. We study the interplay between protein-protein and protein-chromatin interactions, and the resulting condensates which arise due to liquid-liquid phase separation, or a via a bridging-induced attraction mechanism. For proteins which interact multivalently, we obtain a phase diagram which includes liquid-like droplets, droplets with absorbed polymer, and coated polymer regimes. Of particular interest is a regime where protein droplets only form due to interaction with the polymer; here, unlike a standard phase separating system, droplet density rather than size varies with the overall protein concentration. We also observe that protein dynamics within droplets slow down as chromatin is absorbed. If the protein-protein interactions have a strictly limited valence, fractal or gel-like condensates are instead observed. Together this provides biologically relevant insights into the nature of protein-chromatin condensates in living cells.
Non-equilibrium phase separating systems with reactions can break time-reversal symmetry (TRS) in two distinct ways. Firstly, the conservative and non-conservative sectors of the dynamics can be governed by incompatible free energies; when both sectors are present, this is the leading-order TRS violation, captured in its simplest form by Model AB. Second, the diffusive dynamics can break TRS in its own right. This happens only at higher order in the gradient expansion (but is the leading behaviour without reactions present) and is captured by Active Model B+ (AMB+). Each of the two mechanisms can lead to microphase separation, by quite different routes. Here we introduce Model AB+, for which both mechanisms are simultaneously present, and show that for slow reaction rates the system can undergo a new type of hierarchical microphase separation, whereby a continuous phase of fluid 1 contains large droplets of fluid 2 within which small droplets of fluid 1 are continuously created and then absorbed into the surrounding fluid-1 phase. In this state of bubbly microphase separation the small-scale 1-in-2 droplets arise by the conservative diffusive dynamics with the larger scale 2-in-1 structure governed by the nonconservative reactions.
We study the liquid-liquid phase separation (LLPS) of a cell-free transcription-translation (TXTL) system. When the TXTL reaction, composed of a large amount of proteins, is concentrated, the uniformly mixed state becomes unstable and membrane-less droplets form spontaneously. This LLPS droplet formation can be induced when the TXTL reaction is enclosed in water-in-oil emulsion droplets in which water evaporates (dehydration) from the surface. As the emulsion droplets shrink, smaller LLPS droplets appear inside the emulsion droplets and coalesce into phase-separated domains that partition the location of proteins. We show that the LLPS in the emulsion droplets can be accelerated by interfacial drift in the outer oil phase. This further provides an experimental platform for studying the interplay between biological reactions and intracellular phase separation.
As a result of nonequilibrium forces, purely repulsive self-propelled particles undergo macrophase separation between a dense and a dilute phase. We present a thorough study of the ordering kinetics of such motility-induced phase separation (MIPS) in active Brownian particles in two dimensions, and we show that it is generically accompanied by microphase separation. The growth of the dense phase follows a law akin to the one of liquid-gas phase separation. However, it is made of a mosaic of hexatic microdomains whose size does not coarsen indefinitely, leaving behind a network of extended topological defects from which microscopic dilute bubbles arise. The characteristic length of these finite-size structures increases with activity, independently of the choice of initial conditions.
The performance of a molecular motor, characterized by its power output and energy efficiency, is investigated in the motor design space spanned by the stepping rate function and the motor-track interaction potential. Analytic results and simulations show that a gating mechanism that restricts forward stepping in a narrow window in configuration space is needed for generating high power at physiologically relevant loads. By deriving general thermodynamics laws for nonequilibrium motors, we find that the maximum torque (force) at stall is less than its theoretical limit for any realistic motor-track interactions due to speed fluctuations. Our study reveals a tradeoff for the motor- track interaction: while a strong interaction generates a high power output for forward steps, it also leads to a higher probability of wasteful spontaneous back steps. Our analysis and simulations show that this tradeoff sets a fundamental limit to the maximum motor efficiency in the presence of spontaneous back steps, i.e., loose-coupling. Balancing this tradeoff leads to an optimal design of the motor-track interaction for achieving a maximum efficiency close to 1 for realistic motors that are not perfectly coupled with the energy source.Comparison with existing data and suggestions for future experiments are discussed.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
