Figure 8. General model for Hsp70 mechano-chemical cycle.

Step 1: J co-chaperone loads Hsp70 on substrate, close to a structural wall where entropic pulling/pushing forces are strongest. Step 2: Collisions/repulsion between Hsp70 and the wall push Hsp70 and the associated substrate away from the wall, but with increasing distance the repulsive interactions, frequency of collisions and force diminish so movement stalls (the F vs. d exponential decay curve is adapted from¹⁷). Step 3: A NEF unloads Hsp70 from the stalled position, allowing J to again load an Hsp70 close to the wall so the cycle can continue. Step 1b: If the substrate does not yield to the force exerted by a single Hsp70 then the Hsp70 persists near the J co-chaperone, allowing the latter to load additional Hsp70s onto the first so as to augment the force that is generated.