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

Authors

Nunes Vicente, F., Jawahar, A., Wassermair, M., Rahimi, M., Dzementsei, A., Kräter, M., Fischer, L., Tesoro-Moreno, R., Vauleon, B., Guck, J., Saric, A., Palaia, I., Piel, M., Du Roure, O., Heuvingh, J., Diz-Munoz, A.

Abstract

Cell shape changes during migration, division, or differentiation require the dynamic regulation of actin network mechanics. Actin crosslinkers are central to this regulation, controlling network connectivity and the transmission of contractile forces. A large diversity of crosslinkers exists, differing in length, domain structure, and binding kinetics, yet why cells deploy specific crosslinkers in a physiological context remains unclear. To bridge this gap, we developed a light-controlled actin crosslinker toolbox spanning three physiologically relevant lengths: ~9 nm (fascin-like), ~16 nm (fimbrin-like), and ~56 nm (alpha-actinin-like). Using magnetic pincher experiments and in silico modelling, we show that short and mid-length crosslinkers dynamically tune cortical stiffness and thickness in a density- and myosin-dependent manner, with short crosslinkers also driving pronounced stress-stiffening as the cortex is deformed. Strikingly, minute-scale activation reveals a length-dependent switch in cell behaviour: short crosslinkers cause cortical delamination, while long ones instead drive cell polarization and symmetry breaking. This switch can be overridden by perturbing actin turnover, which unlocks polarization in mid-length crosslinkers that otherwise delaminate. Crosslinker-induced polarization is not merely a local cortical event: it directs subsequent cell spreading, coupling a nanometre-scale molecular choice to a cell-scale decision about movement. Together, these findings establish a versatile optogenetic platform for manipulating actin crosslinking, and show that the cortex can encode a behavioural switch directly in its material architecture.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 01 Sep 2026.

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