Optogenetic control of actin crosslinker length reveals a mechanical basis for cortical symmetry breaking

Actin networks play a crucial role in regulating cell shape changes during various cellular processes. Actin crosslinkers, which differ in length, structure, and binding kinetics, are essential for controlling network connectivity and the transmission of contractile forces. However, the specific deployment of crosslinkers in physiological contexts is still not well understood.

To address this knowledge gap, a research team developed a light-controlled actin crosslinker toolbox with three relevant lengths: ~9 nm (fascin-like), ~16 nm (fimbrin-like), and ~56 nm (alpha-actinin-like).

Through magnetic pincher experiments and computer simulations, the researchers demonstrated that short and mid-length crosslinkers can dynamically adjust cortical stiffness and thickness. Short crosslinkers also induce stress-stiffening as the cortex is deformed. Surprisingly, even a small activation of crosslinkers reveals a length-dependent switch in cell behavior.

Short crosslinkers lead to cortical delamination, while long crosslinkers promote cell polarization and symmetry breaking. This switch can be counteracted by disrupting actin turnover, which enables polarization in mid-length crosslinkers that would otherwise delaminate.

The impact of crosslinker-induced polarization extends beyond the local cortical region. It directly influences subsequent cell spreading, linking a molecular choice at the nanoscale to a cell-scale decision about movement. These findings establish an adaptable optogenetic platform for manipulating actin crosslinking and reveal that the cortex can encode a behavioral switch directly within its material architecture.