Interplay of Stochastic Processes during Actin Depolymerization

Abstract

The dynamic polymerization (assembly) and depolymerization (disassembly) of actin filaments are pivotal for cell motility, cell adhesion, and cell division. The hydrolysis of actin-bound ATP destabilizes the filaments over time by enhancing the depolymerization velocity. However, abrupt changes of depolymerization were observed in single filament experiments, which were interpreted in terms of global structural transitions leading to increased filament stability with aging [Kueh et al. (2009), Science 325: 960]. In contrast to this proposal, we have demonstrated that these interruptions are caused by local transitions which turned out to be the photo-induced dimerization of neighboring filament subunits [Niedermayer et al. (2012), PNAS 109: 10769]. Here, we discuss and generalize the idea that led to this crucial notion of local transitions within the filaments. The time from the initiation of depolymerization until the occurrence of the first interruption represents a stochastic variable and the distribution function of this variable is a fingerprint of the unknown transition mechanism. By modeling the underlying stochastic processes - association and dissociation of actin subunits as well as hypothetical transitions -, we compute the distribution functions for many possible transition mechanisms and compare these functions to experimental data. We also generalize our theoretical description to accommodate for instance finite size effects or the influence of ATP hydrolysis. Furthermore, we outline how stochastic modeling may help deciphering other fundamental issues in actin dynamics.