Sun, Z. G.; Murrell, M.; Vlassak, J.; Zheng, J.; Tabatabai, A. P.

In non-equilibrium (active) systems, increased driving is commonly assumed to amplify energy dissipation. This frames the efficiency of protein-based machines as a fixed or monotonically decreasing function with driving. Using picowatt-sensitive calorimetry and advanced entropy production metrics in reconstituted actomyosin networks, we show that energy dissipation depends non-monotonically on myosin-generated stress (driving). At low driving, dissipation increases proportionally with stress, consistent with near-equilibrium linear response. At high driving, however, dissipation decreases, revealing a far-from-equilibrium regime in which excessive load suppresses motor ATPase activity. This non-monotonicity reflects a transition from spatially localized stress at low driving to delocalized stress at high driving, where force per motor, and thus ATPase suppression, is maximized. Crosslinker mechanics tune this transition as fascin (slip bonds) amplifies stress localization and shifts the dissipation peak to higher driving, whereas -actinin (catch bonds) stabilizes under load, delocalizes stress, and shifts the peak to lower driving. Thus, enhanced mechanochemical coupling causes additional driving to restructure rather than amplify dissipation, revealing how material system organization (bonding), and not driving alone, governs energy flow far from equilibrium.