Charakterisierung und Analyse der physikalischen Mechanismen zur Ausbildung von Membranausstülpungen in biologischen Zellen
Zusammenfassung der Projektergebnisse
Tubular membrane protrusions are generated by cells for normal development and healthy function. In many important situations, the necessary driving force for their formation is provided by the directed polymerization of the filamentous protein actin in combination with other accessory proteins into network structures. Seemingly contradictory experimental results have reported the role of different accessory proteins to be dominant in this context. To clarify and quantify necessary conditions for protrusion formation, we employed a conceptually non-traditional theoretical approach: By considering only a minimum set of proteins required for linear protrusion formation, rather than all accessory proteins that might be involved, we have been focusing on the physical constraints that enable protrusion. For this purpose, we have developed a novel grand canonical simulation of a fluctuating biological membrane, based on a randomly triangulated surface. Implicitly coupling the membrane to a lipid reservoir makes our model applicable to biological processes in which the relevant membrane area changes quasistatically. By additionally including structurally fluctuating and stochastically polymerizing semiflexible filaments into the model, we were able to identify necessary physical conditions and dynamical bottlenecks on the way to actin-driven cell membrane protrusion. Analysis ofthe biophysical simulation as well as a simplified model for analytical progress revealed a membrane mediated dynamical transition from individually polymerizing single filaments to cooperative bundles without the necessity for explicit bundling proteins. Once formed, these bundles efficiently drive tubular extension. Immobile adhesion points ofthe membrane that constrain its height fluctuations, screen the effective attractive interactions between filaments and significantly delay bundling and tube formation.
