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Jun Wu
- Advisor:
- Tanmay Lele (University of Florida), Deborah Leckband (Postdoc Advisor)
- Departments:
- Areas of Expertise:
- cytoskeleton mechanics
- cell nuclear mechanics
- cell mechanotransduction
- cell-cell adhesion
- Thesis Title:
- MOLECULAR MOTOR FORCES AND NUCLEAR POSITIONING IN LIVING CELLS
- Thesis abstract:
- The nucleus is the largest and heaviest organelle in a cell and its proper positioning is crucial for basic cell functions, such as cell migration, division, fertilization and establishment of polarity. Irregularities in nuclear movement (or nuclear positioning) are associated with various serious diseases. Nuclear movement in the cell is a complex process that involves interactions with all three cytoskeletal systems - actin, intermediate filaments and microtubules. The interactions occur through nuclear-embedded molecular tethers that link to the cytoskeleton. The molecular linkage between the nucleus and the cytoskeleton can be also established through molecular motors, proteins that convert chemical energy to mechanical forces. How molecular motors drive nuclear movement remains poorly understood. Nuclear rotation and nuclear translation are the two types of nuclear motions commonly observed in the cell. We investigated the physical mechanism for nuclear rotation in the cell. We found that the nuclear rotation angle is directionally persistent on a time scale of tens of minutes, but rotationally diffusive on longer time scales, and rotation required the activity of the microtubule motor dynein. Based on these results, a mechanical model for torque generation on the nucleus was proposed. To investigate nuclear translation, we designed experiments utilizing two different techniques- protein photo activation and cell micromanipulation. The results from these experiments point to a tug of war between forward pulling and rearward pulling forces on the nuclear surface generated by actomyosin contraction. Net nuclear motion occurs when the forward pulling force increases during lamellipodial formation. We also investigated the mechanisms of positioning of the centrosome, which is in physical proximity with the nucleus. The positioning of centrosome is very important in cell migration and cell division. Whether the centrosome is positioned by pulling forces or pushing forces originating in dynamic microtubules remains a controversy. By severing a single microtubule with femtosecond laser ablation, we found that microtubules are under tension generated by dynein. We also show that dynein-mediated pulling forces are sufficient to center the centrosome.
- Downloads:
Contact information:
junw@illinois.edu