Moving Cell Boundaries Drive Nuclear Shaping during Cell Spreading. Academic Article uri icon

abstract

  • The nucleus has a smooth, regular appearance in normal cells, and its shape is greatly altered in human pathologies. Yet, how the cell establishes nuclear shape is not well understood. We imaged the dynamics of nuclear shaping in NIH3T3 fibroblasts. Nuclei translated toward the substratum and began flattening during the early stages of cell spreading. Initially, nuclear height and width correlated with the degree of cell spreading, but over time, reached steady-state values even as the cell continued to spread. Actomyosin activity, actomyosin bundles, microtubules, and intermediate filaments, as well as the LINC complex, were all dispensable for nuclear flattening as long as the cell could spread. Inhibition of actin polymerization as well as myosin light chain kinase with the drug ML7 limited both the initial spreading of cells and flattening of nuclei, and for well-spread cells, inhibition of myosin-II ATPase with the drug blebbistatin decreased cell spreading with associated nuclear rounding. Together, these results show that cell spreading is necessary and sufficient to drive nuclear flattening under a wide range of conditions, including in the presence or absence of myosin activity. To explain this observation, we propose a computational model for nuclear and cell mechanics that shows how frictional transmission of stress from the moving cell boundaries to the nuclear surface shapes the nucleus during early cell spreading. Our results point to a surprisingly simple mechanical system in cells for establishing nuclear shapes.

published proceedings

  • Biophys J

altmetric score

  • 0.75

author list (cited authors)

  • Li, Y., Lovett, D., Zhang, Q., Neelam, S., Kuchibhotla, R. A., Zhu, R., ... Dickinson, R. B.

citation count

  • 75

complete list of authors

  • Li, Yuan||Lovett, David||Zhang, Qiao||Neelam, Srujana||Kuchibhotla, Ram Anirudh||Zhu, Ruijun||Gundersen, Gregg G||Lele, Tanmay P||Dickinson, Richard B

publication date

  • August 2015