The cell’s ability to generate, sense, and respond to mechanical force is crucial in many biological processes, including cell division and differentiation. Our laboratory takes a multi-disciplinary approach, integrating biophysical micromanipulation tools (e.g., optical tweezers, glass microfibers) with biochemical perturbation, single-molecule imaging, and material science methods to study how the spindle – the chromosome segregation machinery – can assemble into a proper size and shape and generate and respond to forces for error-free cell division. We also use our micromanipulation technique to analyze the mechanical integrity of the nucleus.
Images show micromanipulation experiments performed in our laboratory for examining the micromechanical properties of the spindle (A) and the cell nucleus (B). Using microneedle-based force probes (white arrowheads) and high-resolution microscopy, we study how these structures generate and respond to forces while properly functioning in a cell.
Takagi J, Sakamoto R, Shiratsuchi G, Maeda YT, Shimamoto Y. Mechanically Distinct Microtubule Arrays Determine the Length and Force Response of the Meiotic Spindle. Dev Cell. 2019 Apr 22;49(2):267-278.e5.
Shimamoto Y, Tamura S, Masumoto H, Maeshima K. Nucleosome-nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity. Mol Biol Cell. 2017 Jun 1;28(11):1580-1589.
Takagi J, Shimamoto Y. High-quality frozen extracts of Xenopus laevis eggs reveal size-dependent control of metaphase spindle micromechanics. Mol Biol Cell. 2017 Aug 1;28(16):2170-2177.
Shimamoto Y, Forth S, Kapoor TM. Measuring Pushing and Braking Forces Generated by Ensembles of Kinesin-5 Crosslinking Two Microtubules. Dev Cell. 2015 Sep 28;34(6):669-81.