Person:

Levine, Erel

Self-organization in the cell relies on the rapid and specific binding of molecules to their cognate targets. Correct bindings must be stable enough to promote the desired function even in the crowded and fluctuating cellular environment. In systems with many nearly matched targets, rapid and stringent formation of stable products is challenging. Mechanisms that overcome this challenge have been previously proposed, including separating the process into multiple stages; however, how particular in vivo systems overcome the challenge remains unclear. Here we consider a kinetic system, inspired by homology dependent pairing between double stranded DNA in bacteria. By considering a simplified tractable model, we identify different homology testing stages that naturally occur in the system. In particular, we first model dsDNA molecules as short rigid rods containing periodically spaced binding sites. The interaction begins when the centers of two rods collide at a random angle. For most collision angles, the interaction energy is weak because only a few binding sites near the collision point contribute significantly to the binding energy. We show that most incorrect pairings are rapidly rejected at this stage. In rare cases, the two rods enter a second stage by rotating into parallel alignment. While rotation increases the stability of matched and nearly matched pairings, subsequent rotational fluctuations reduce kinetic trapping. Finally, in vivo chromosome are much longer than the persistence length of dsDNA, so we extended the model to include multiple parallel collisions between long dsDNA molecules, and find that those additional interactions can greatly accelerate the searching.

Unlike most macromolecules that are homogeneously distributed in the bacterial cell, mRNAs that encode inner-membrane proteins can be concentrated near the inner membrane. Cotranslational insertion of the nascent peptide into the membrane brings the translating ribosome and the mRNA close to the membrane. This suggests that kinetic properties of translation can determine the spatial organization of these mRNAs and proteins, which can be modulated through posttranscriptional regulation. Here we use a simple stochastic model of translation to characterize the effect of mRNA properties on the dynamics and statistics of its spatial distribution. We show that a combination of the rate of translation initiation, the availability of secretory apparatuses, and the composition of the coding region determines the abundance of mRNAs near the membrane, as well as their residence time. We propose that the spatiotemporal dynamics of mRNAs can give rise to protein clusters on the membrane and determine their size distribution.