The cytoskeleton is a complex and highly dynamic network of protein filaments, motors, regulatory agents - such as cross-linkers or bundlers - and membranes, that gives eukaryotic cells their shape and mechanical strength and drives dynamic cell functions such as cell locomotion, division, and growth.
I will explore how the microscopic structure and the active and passive dynamics of the cytoskeleton determine cellular mechanics. I aim towards a quantitative physical understanding of the molecular mechanisms of dynamic cell functions. This requires a dual approach, integrating in vitro studies of active cytoskeletal protein networks with in vivo investigations of cells.
The influences of cross-linking and motor proteins on the microstructure and micromechanics of cytoskeletal networks will be studied using networks of reconstituted actin filaments. I will compare bundled and isotropically cross-linked actin networks, and study the non-equilibrium properties created by the activity of tension-generating motor proteins.
Since the cytoskeleton is intrinsically heterogeneous it will be essential to use and develop microrheological techniques that can resolve local variations of mechanical properties on a micrometer scale. Colloidal probe particles will be inserted into in vitro networks and living cells (endothelial cells, fibroblasts, osteocytes, and neurons), and their thermal motion will be monitored with light microscopy, laser interferometry, and diffusing wave spectroscopy.
I will use active manipulation of the probe particles with optical tweezers to examine the non-linear regime of the viscoelastic response. The project is highly interdisciplinary, since it integrates cell biology and biochemistry with soft condensed matter and polymer physics, statistical mechanics, and cutting-edge optical technology.
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