Unexpected Low Mechanical Stability of Titin I27 Domain at Physiologically Relevant Temperature

The extensively studied immunoglobulin (Ig) domain I27 of the giant force-bearing protein titin has provided a basis for our current understanding of the structural stability, dynamics, and function of the numerous mechanically stretched Ig domains in the force-bearing I-band of titin. The current consensus is that titin I27 has a high mechanical stability characterized by very low unfolding rate (<10^-3 s^-1) in physiological force range and high unfolding forces (>100 pN) at typical physiological force loading rates from experiments at typical laboratory temperatures. Here, we report that when the temperature is increased from 23 to 37 °C, the unfolding rate of I27 drastically increases by ∼100-fold at the physiological level of forces, indicating a low mechanical stability of I27 at physiological conditions. The result provides new insights into the structural states and the associated functions of I27 and other similar titin I-band Ig domains.