Cell Mechanics and Motility: Controlling Intracellular Transport with Micropatterns.

摘要

A thorough understanding of molecular interactions and transport governing cell mechanics and motility is necessary for the ultimate goal of improving human health, such as the development of cancer diagnostics and cancer treatment. However, despite decades of research and advances in biological experimental techniques, the intricate molecular mechanisms are still incompletely understood, making prediction and control of cells almost impossible.;One non-invasive way to study the internal organization of a cell is by constraining the cell on surface micropatterns of desired geometries. Micropatterns with effectively designed geometries can be used to understand and control cell mechanics and motility in three different ways: (1) Confining cells on micropatterns with fixed geometries prevent cells from assuming irregular shapes, making quantification and averaging across cells possible. Continuous 2D imaging of the cells through time shows that cells eventually depolarize on both symmetric and asymmetric micropatterns. Using confocal microscopy, 3D reconstruction of cell shapes on circular micropatterns revealed that the main components regulating cell shape and mechanics are cortical actin, cell membrane and nucleus. (2) Micropatterns with "designed" geometries also enable spatial separation of cellular components (e.g. focal adhesion and cytoskeleton, such as actin bundles and microtubules). For instance, cells on triangular micropatterns enable focal adhesion to be concentrated on the vertices while actin bundles form on the edges. Interestingly, live-cell imaging shows a cell-wide targeting of microtubules toward focal adhesion, guided by actin bundles. Furthermore, if the triangular micropatterns are connected in a linear chain, the asymmetric geometry could bias motion of cells in one direction, creating a ratcheting effect. (3) Confining cells on micropatterns (e.g. on linear tracks) allow a "reduction in dimensionality" for the migrating cells. Analysis of cellular trajectories along linear tracks shows that cancerous, non-metastatic cells move diffusively, while cancerous, metastatic cells move super-diffusively. Power-law distribution of the trajectories indicates that the metastatic cells are undergoing Levy walk, an optimum strategy for searching remote targets.