Sensorimotor and Molecular Mechanisms of Non-Contact ACL Injury: An Integrative Hypothesis

Non-contact anterior cruciate ligament (ACL) ruptures occur in the blink of an eye: peak ligament strain usually coincides with the first 30-50 ms after foot strike, long before reflex feedback can intervene. The model proposed herein integrates findings from previously published studies to formulate a testable framework. The proposed model assigns the decisive protective role to feed-forward hamstring tension and the calcium-dependent stiffening of titin, both of which are fully established before ground contact. Once impact occurs, short-range muscle stiffness and residual force enhancement dominate load absorption, but their buffering capacity is finite; if anterior shear and valgus torque exceed this molecular "spring-damper" threshold within ~60 ms, the ACL ruptures. Reflex-mediated hamstring activity arrives ≥35 ms after impact and transcortical corrections even later, rendering feedback too slow for primary protection. By mapping the cascade from cortical pre-activation to titin nano-mechanics, the model clarifies why pre-contact landing strategies and eccentric-strength training are the cornerstones of injury prevention, and it identifies specific molecular adaptations faster Ca²⁺ release, larger titin-actin binding capacity, and enhanced short-range stiffness as novel therapeutic targets. The purpose of this clinical commentary is to provide a theoretical model intended to guide future empirical investigations. # Level of Evidence 5.