The Dynamics of Dorsal Actin Waves

Abstract

The recent years have shown that waves of actin polyermization are central to the morphodynamics of cells. This thesis is dedicated to deciphering of the propagation mechanism underlying actin waves known as Circular Dorsal Ruffles (CDRs). While these ring-shaped undulations on the dorsal cell side have been known to the biological community for several decades the mechanism underlying their formation and propagation has remained a puzzle. It is the hypothesis of this work that CDRs can be described as waves that form and propagate in an active medium that is constituted by the actin machinery of the cell. The identification of the corresponding functional elements is the aim of this work. For this, the structure, morphology and dynamics of CDRs are investigated in detail and with a view that is guided by the typical structure of models of active media. Throughout the whole thesis, the FitzHugh-Nagumo system serves as a prototype model for the explanation of the mechanisms underlying the phenomena observed for CDRs on an abstract level. Novel results are presented regarding the identification of the processes of actin dynamics within CDRs and their compartmentalization. The systematic analysis of the dynamics of CDR wavefronts reveals that they exhibit a number of previously unknown phenomena, among them breathing modes, spiral waves, and collision annihilation. All these features are well founded in the framework of active media. Since the dynamics of CDRs strongly depends on the cellular morphology, a novel method for their investigation is developed in which cells are forced into disc-shapes via microcontact printing for a quantitative analysis of data of identically shaped cells. This framework allows for direct comparability to numerical studies, which reveals that stochastic elements in protein dynamics are key for the understanding of CDRs.