Mechanical forces promote actin-mediated structural plasticity

Neurons encode memory through the strengthening of their connections (synapses). A long-lasting synaptic strength increase correlates with an increase in the size of the dendritic spines, where the postsynapse is located. During four minutes after stimulation, spines transiently enlarge over three times their original size, which is only possible through a reconfiguration of the actin cytoskeleton. Upon stimulation, dendritic spines undergo a series of chemical reactions, and there is a stimulus-triggered influx of actin and actin-binding proteins into the spines, which promote rapid remodeling of the actin cytoskeleton. However, the huge diversity and amount of proteins inside the spines hinder the understanding of the underlying mechanisms. Here, we developed a minimal 3D model of dendritic spines describing actin, Arp2/3, and cofilin dynamics with partial differential equations in a moving boundary framework. Boundary evolution arises from the interaction between the force generated by actin polymerization and the force generated by the spine membrane, which counteracts deformations. Using this framework, we investigate: 1) If this reduced model is enough to qualitatively reproduce the increase in spine size upon stimulation. 2) If spatial localization of the stimulus-triggered influx translates into a more efficient spine size increase. 3) If other mechanical forces promote spine expansion. The latter is inspired by recent experiments showing that clutch molecules bind actin filaments to extracellular elements, thereby reducing their retrograde flow and increasing spine enlargement. We find that the reduced model is enough to mimic the spine expansion. Moreover, localization of the stimulus-triggered influx of proteins translates into a more efficient spine enlargement. However, there is a limit to spine growth due to the counteracting membrane force. We find that further spine expansion is only possible by introducing other mechanical forces to the model produced by clutch molecules and the presynaptic bouton.