Mechanisms for directed transport and organization at subcellular scales

Synopsis

The timely and faithful segregation of genetic material is an essential cellular function that relies on the transport and stable positioning of subcellular components despite the disruptive influence of thermal fluctuations. In prokaryotes, a two-protein system (known as ParABS) has been identified as being responsible for the positioning of low-copy number plasmids and chromosomes prior to cell division. Multiple experimental observations, in vitro reconstitutions and computational modelling efforts support the idea that this system is powered by the ‘burnt-bridge’ Brownian ratchet mechanism. In this thesis we provide computational models that complement these studies to understand how this mechanism generates and sustains directional transportation through the transduction of chemical energy into mechanical motion. In particular we study the effects of chemical kinetics, system size, the conformational state and availability of proteins that drive this mechanism with an application to the rich protein dynamics observed in vivo. Ultimately, we simulate a coarse-grained model for a highly polyvalent ‘burnt-bridges’ Brownian ratchet capable of translocating either by rotation or translation and detail the system parameters that govern the transitions between these two distinct modes of motion. The models presented in this thesis provide key insights and make experimentally testable predictions which can be used for the engineering of novel synthetic motor systems.