Force writes memory: proline isomerization as a molecular memory switch

Mechanical forces play a pivotal role in cellular processes, acting as molecular switches that encode, store, and retrieve information, thereby facilitating a form of molecular memory. This review explores how protein unfolding and refolding under tensile loads generate history-dependent responses that regulate domain stability and function. We focus on proline isomerization as a reversible switch, enabling distinct quasi-stable states that underpin medium- to long-term mechanical memory. Leveraging insights from molecular dynamics simulations and experimental data, we propose that proline isomerization creates a graded, adaptive memory response, distinct from binary on-off switches, with implications for biomaterial design and biorobotics. This mechanism offers a framework for developing force-responsive materials with memory properties, enhancing applications in tissue engineering and soft robotics.