Figure 7.

A concept model of mechano-homeostasis and dyshomeostasis leading to whole-scale synaptic changes. (a,b) In the MeshCODE theory of a mechanical basis of memory, the synaptic scaffold protein talin is a memory molecule. The 13 force-dependent binary switches in the talin rod can store information in a binary format that spatially organizes the synaptic enzymes to control synaptic activity. (a) In a normal synapse, the scaffolding controls the synaptic activity as a function of the talin switch patterns. The connection of talin to the membrane involves APP (red) and the focal adhesion complex containing integrin (blue) and kindlin (orange). (b) Perturbed mechanical cues and destabilization of the adhesion complex lead to increased APP processing and loss of the APP-talin connection. The information written in the shape of the talin molecule is lost as it is no longer under tension and the molecule resets. (c) The coupling of the force-generation machinery to the synaptic cleft provides a way to control the synaptic activity as a function of the switch patterns organizing the synaptic enzymes differently. However, as each APP is cleaved, a connection of the cytoskeleton to the synaptic cleft is severed, leading to loss of information but also to dyshomeostasis. Ultimately, the loss of mechanical couplings leads to the death of the synapse.