Living cells are endowed with structure and mechanical stability by an intricate elastic network of protein filaments known as the cytoskeleton. These filaments are stiff on the scale of the cell and thus readily deform the cell membrane, while simultaneously being affected configurationally by spatial confinement. The coupled morphogenesis of cytoskeleton and membrane ultimately appears as dynamic rearrangements that drive physiological processes such as cell migration or division. I strive to unravel biophysical principles of cell morphogenesis. To this end, I propose to construct biomimetic cell models by confining actin biopolymer gels to cell-sized lipid vesicles mimicking cellular confinement. I will systematically investigate the interplay between entropy-driven organization, and that induced by cross-linker proteins which connect actin filaments, or motor proteins which actively slide them. A key innovation lies in the bottom-up approach of gradually increasing system complexity to eventually achieve a model which is far more realistic than existing assays. The system permits quantitative measurements of network and membrane shape (using fluorescence microscopy) and of local and global mechanical properties as well as active driving (using innovative particle tracking microrheology). This will allow me testing and development of new theoretical models. The proposed project promises to significantly advance our understanding of how cells orchestrate their shape and movements, and to foster novel medical treatments of diseases related to malfunctions of the cytoskeleton. Simultaneously, it addresses exciting physical questions raised by the unusual properties of cells, such as self-organization of non-equilibrium soft matter and material properties of polymer-membrane composites. If we can identify physical design principles of cells we can eventually harness these to create novel functional and smart materials based on bio(-inspired) molecules.
Field of science
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
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