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Mason N. Rouches

Publications and source records attributed to Mason N. Rouches.

2 recordsLinked to original sources

Decoding molecular distributional codes through collective instabilities

Biological information is often encoded in molecular variants that differ in just a few chemical traits, such as the number of phosphorylated sites or ubiquitin chain length, rather than in arbitrarily distinct species. These molecular distributions carry information about cellular state, yet reading them with conventional molecular circuits requires prohibitively many distinct sensors. In contrast, we show that collective physical instabilities can naturally integrate the information encoded in such distributions. Using an information-theoretic matching condition between an encoded distribution and a physical readout, we derive a geometric condition that any good decoder must satisfy, and establish that phase separation, percolation, and membrane curvature instabilities all approach it for biologically natural distributions while simple mass-action binding does not. Using mean-field theory and lattice Monte Carlo simulations, we find that phase separation reads the shape of a distribution beyond its mean, robustly capturing its variance and, more weakly, its skewness, whereas mass-action binding detects only the mean. Near phase boundaries the readout captures nearly all the information present in the molecular population. Finite valency, through the threshold for network formation, adds discriminatory power invisible to mean-field theory. These results suggest that cells can exploit collective physical instabilities as natural, compact, yet near-optimal sensors for decoding molecular distributional codes.

physics.bio-ph↗

Protein-DNA Co-condensation is Prewetting to a Collapsed Polymer

The three-dimensional organization of chromatin is thought to play an important role in controlling gene expression. Specificity in expression is achieved through the interaction of transcription factors and other nuclear proteins with particular sequences of DNA. At unphysiological concentrations many of these nuclear proteins can phase-separate in the absence of DNA, and it has been hypothesized that, in vivo, the thermodynamic forces driving these phases help determine chromosomal organization. However it is unclear how DNA, itself a long polymer subject to configurational transitions, interacts with three-dimensional protein phases. Here we show that a long compressible polymer can be coupled to interacting protein mixtures, leading to a generalized prewetting transition where polymer collapse is coincident with a locally stabilized liquid droplet. We use lattice Monte-Carlo simulations and a mean-field theory to show that these phases can be stable even in regimes where both polymer collapse and coexisting liquid phases are unstable in isolation, and that these new transitions can be either abrupt or continuous. For polymers with internal linear structure we further show that changes in the concentration of bulk components can lead to changes in three-dimensional polymer structure. In the nucleus there are many distinct proteins that interact with many different regions of chromatin, potentially giving rise to many different Prewet phases. The simple systems we consider here highlight chromatin's role as a lower-dimensional surface whose interactions with proteins are required for these novel phases.

physics.bio-ph↗