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Active biomimetic systems

Final Report Summary - ACTIVE BIOMICS (Active Biomimetic Systems)

The project consisted of six scientific work packages (WPs) aimed at studying in detail the different aspects of active biomimetic systems.

WP1: Force generation by actin filaments. Understanding the molecular mechanisms of site-directed growth and force-generation by actin filaments (LEBS, MPI, ULEIP). The focus of this WP was on:
- Site-directed growth of filament bundles;
- Motor properties of formin;
- Actin network in vesicles and liposomes;
- Coordinated actin turnover.

WP2: Force generation by microtubules. Theoretical and experimental studies of force generation by single and bundled microtubules. The focus of this WP was on:
- Single microtubules, effects of regulatory proteins;
- Microtubule bundles, experiments;
- Microtubule bundles, theory and modeling.

WP3: Force generation by stepping motors. Experimental and Theoretical study of force generation by single motors. The focus of this WP was on:
- Regulation of force generation;
- Molecular mechanics of stepping motors;
- Membrane tubes pulled out by kinesin motors.

WP4: Transport by stepping motors. Experimental and theoretical studies of transport by stepping motors on immobilised and growing filaments. The focus of this WP was on:
- Motor traffic on immobilized filaments, experiment and theory;
- Processivity of myosin minifilaments;
- Motor traffic on growing filaments, theory and experiment;
- Transport of kinesin-supported capsules along microtubules.

WP5: Self-Organisation in actin-based systems. Self-organization of actin filaments based on crosslinking by myosin motors in order to generate active biomimetic polymer networks. The focus of this WP was on:
- Architecture of crosslinked actin networks;
- Active actin/myosin bundles;
- Stability/instability and oscillatory behavior of active networks.

WP6: Self-Organization in microtubule-based systems. Active assemblies built up from microtubules and kinesin motors using purified proteins, such as natural molecular motors and artificial, designed motors. The focus of this WP was on:
- Self-organized assemblies and pre-structured environments, experiments;
- Regulation of self-organized assemblies, experiments;
- Numerical simulations and theory.

Experiments were performed to describe the force generation of thick bundles of actin filaments and their site-directed nucleation by surface anchored molecules. In addition, measurements at the mesoscopic scale provided further insight into the molecular mechanisms underlying motility.

In order to elucidate the transport properties within cells, the molecular motor kinesin was studied in great detail. On the one hand, the kinesin/microtubule interaction was studied using molecular modelling and was shown to depend on the state of the nucleotide binding pocket of the molecular motor. On the other hand, the molecular structure of kinesin's motor head was also addressed from the experimental side. By using recombinant methods, it was possible to modify this structure and to elucidate the interplay between the nucleotide binding pocket and the microtubule binding domain.

The behaviour of kinesin in crowded environments was studied and its ability to bypass obstacles was observed on the microtubule. On the other hand, it was demonstrated that kinesins, when immobilized on a structured surface, pull microtubules over this surface with a gliding velocity that can be controlled by the motor density.

Models that represented a rather general molecular mechanism for the bi-directional transport of cargo were developed.

Both actin filaments and myosin motors are essential parts of the mechanisms underlying muscular contraction. During the project several biomimetic systems by which one can study the interplay between actin filaments and myosin motors at the nanometer scale were built.