Compressive force from the nuclear envelope in dividing S. pombe alters binding of mitotic spindle proteins and...

During closed mitosis in S. pombe, the nuclear envelope and mitotic spindle must work together to ensure successful nuclear division. Previous work has demonstrated that mechanical force from the nuclear envelope, transmitted through spindle pole bodies, can reshape the spindle. However, it remains unclear how force from the nuclear envelope might regulate binding or other biochemical properties of microtubule associated proteins (MAPs) in the spindle. Here, we investigate how force reprograms the spindle with two approaches: chronically increasing nuclear envelope tension via the lipid synthesis inhibitor cerulenin, and acutely applying force to the nucleus through an optical trap. Both perturbations slow spindle elongation dynamics and reduce microtubule density. Despite this reduction, key spindle proteins Ase1 and Klp5 increase their density at the spindle midzone, indicating inward force from the nuclear envelope can alter MAP binding in the spindle. We find that while motor proteins Klp5 and Klp6 only minimally affect the spindle's response to increased nuclear envelope force, the combination of removing Ase1 and increasing nuclear envelope force together rescues spindle microtubule stability. Together, our findings reveal that nuclear force on the spindle does not merely alter its shape, but is key in regulating its biochemistry to maintain force balance and ensure cellular function.