The physical basis for actin-driven cell membrane protrusions

• Applicant: Dr. Julian Weichsel
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2011 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 204391879

Membrane protrusions are generated by cells for normal development and healthy function. 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-like structures. Distinct types of characteristic protrusions are classified according to their geometric shape and the architecture of the actin network they contain. However, the necessary physiological conditions for their formation and differentiation are not sufficiently understood. Recently, seemingly contradictory results have emerged, which reported the role of different accessory proteins to be dominant in this context. In this proposal, we will contribute in resolving this current controversy. In a conceptually nontraditional approach, we will focus on the physical constraints that enable protrusions rather than on the individual accessory proteins involved. By developing a comprehensive biophysical simulation of actin network growth against a deformable biological membrane, we will identify and characterize physical conditions that facilitate protrusion. Subsequently, the theoretical predictions of the model will be interpreted using knowledge of the expected action of different accessory proteins. In this way, specific predictions of the model will be tested by our collaborators within reconstituted in-vitro experiments using purified proteins. Successful completion of this project will (i) produce a physical understanding of protrusion formation and differentiation, (ii) provide testable predictions for the conditions required for protrusion formation based on the physical model parameters, and (iii) explain the role of specific proteins through their expected effect on physical constraints.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Phillip Geissler