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Michael B. Elowitz

Publications and source records attributed to Michael B. Elowitz.

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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

Mutual inactivation of Notch and Delta permits a simple mechanism for lateral inhibition patterning

Lateral inhibition patterns mediated by the Notch-Delta signaling system occur in diverse developmental contexts. These systems are based on an intercellular feedback loop in which Notch activation leads to down-regulation of Delta. However, even in relatively well-characterized systems, the pathway leading from Notch activation to Delta repression often remains elusive. Recent work has shown that cis-interactions between Notch and Delta lead to mutual inactivation of both proteins. Here we show that this type of cis-interaction enables a simpler and more direct mechanism for lateral inhibition feedback than those proposed previously. In this mechanism, Notch signaling directly up-regulates Notch expression, thereby inactivating Delta through the mutual inactivation of Notch and Delta proteins. This mechanism, which we term Simplest Lateral Inhibition by Mutual Inactivation (SLIMI), can implement patterning without requiring any additional genes or regulatory interactions. Moreover, the key interaction of Notch expression in response to Notch signaling has been observed in some systems. Stability analysis and simulation of SLIMI mathematical models show that this lateral inhibition circuit is capable of pattern formation across a broad range of parameter values. These results provide a simple and plausible explanation for lateral inhibition pattern formation during development.

q-bio.MN