Biomechanics of Complex Microtubule Networks

University Of Utah, Salt Lake City UT

Investigators

Abstract

Humans and many other organisms are comprised of cells which possess a complex biomechanical framework: the cytoskeleton. The composition and internal layout of the cytoskeleton is different from cell to cell. Some differences are purely random but there are also clear systematic architectural differences between various cell types. For example, cells involved in diseases (e.g. cancer) often have markedly different cytoskeleton from cells in a healthy organism. It is currently not clear how different cytoskeletal architectures relate to overall cell biomechanical properties. One of the problems hindering progress has been the inability to reproducibly assemble cytoskeletal networks in a controlled environment. However, a recently developed nano-scale assembly technique allows for exactly this: the longest and least flexible cytoskeletal filaments known as microtubules can now be assembled and manipulated with sufficient flexibility and precision to build structures in a controlled environment which mimic what is seen in cells. Research conducted under this award will use this novel approach to examine the biomechanical properties of a number of key biologically relevant filament architectures. The work will also examine how the biomechanics of microtubule cytoskeleton changes when the architecture is identical but the overall size of the filament structure is varied instead. These measurements together will provide both a big picture view (the role of microtubule network architecture in cellular biomechanics) and small scale perspective (how stress propagates across the network). This research will examine several key microtubule network topologies. A recently demonstrated holographic optical trapping approach will be used to assemble microtubule networks in vitro in 3D. Holographic and ordinary trapping will be used together to manipulate and to probe such networks in situ. For a given network layout, this study will also establish how the biomechanical properties of the model network change with overall scale. Therefore, the extent to which select microtubule network architectures contribute to cellular biomechanics will be established. The role of filaments and cross-links with different mechanical properties will also be quantitatively examined using the same experimental technique.