Lipid Nanotube Networks: Shape Transitions and Insights into the Dynamics of Self-Organization

Doctoral thesis, 2007

Nanotube-vesicle networks (NVNs) are simplified models of cell membrane tubular systems which are dynamic transportation routs for molecular cargoes in biological cells. The presented work describes dynamic properties of NVNs such as self-organization, shape and topology transformations; moreover, specific geometric properties of the networks are used for controlling enzymatic reactions. A nanotube-vesicle network is a network of surface-adhered lipid vesicles (5-25 m in radius) connected by suspended lipid nanotubes (100-200 nm in radius). Vesicle size, nanotube length, and connectivity of a network can be controlled with high precision. Initially, the network is trapped in a high free energy state. By proper means, it is possible to trigger network self-organization towards a lower free energy state. Network evolution begins with merging of two adjacent nanotubes, and formation of a single nanotube three-way junction. Based on experimental observations of fluorescently labeled nanotubes and a theoretical model, the nanotube three-way junction is shown to propagate with a zipper-like mechanism, described in Paper I of this thesis. Lipids from two merging branches flow through the junction and form an extension on the third nanotube branch. Depending on the starting arrangement of the nanotubes, a NVN can evolve towards entangled and knotted geometries; or it can form a system of branching nanotubes. Paper II describes the formation of knotted nanotubes. The estimated size of the knot is comparable with the radius of a lipid nanotube. It is also demonstrated that such a knot can be used as a mechanical tweezer to capture and transport submicrometer-sized objects. In the experiments described in Paper III, NVNs are shown to form tree-like structures. The nanotubes arrange into symmetric three-way junctions with angles of 120o between the nanotubes. Moreover, the process of self-organization in the networks reveals a strong similarity with some optimization problems, such as the Euclidian Steiner Tree Problem. Paper IV suggests a method to form circular lipid nanotubes. The presented method gives new opportunities for preparing, manipulating and studying shape transitions of vesicles with non-spherical topology. Finally in Paper V, the geometry of a NVN is used to control the dynamics of an enzymatic reaction. Here, the vesicles are used as containers for reacting molecules, and the nanotubes serve as transportation routes. The narrow nanotube entrances act as transport barriers for the enzyme molecules. In such a reaction-diffusion system, the reaction occurs as a cascade through the containers and displays wave-like behavior.