1The LO simulations make it possible to design novel cardiac muscle contraction models by following iterative approaches 2 where the consequences of model assumptions can be evaluated across scales from isolated preparation assays to whole 3 organ effects. Leveraging such capability, we constructed a new phenomenological model of muscle contraction. The new 4 myofilament model is a modified version of [1] with the addition of XB-XB cooperative effects and with a simple 5 mean-field strain formulation similar to [2]. The model equations are designed to reproduce several experimental features 6 observed in both isolated muscle and physiological measurements at the ventricle level, as described below. 7 XB kinetics and ktr-Ca dependence 8 Similar to previous models describing cooperative behavior of crossbridges (XBs) within regulatory units (RUs) (e.g., [3]), 9 we simulated XB dynamics from the perspective of XB-groups. The core model equation describes the formation and 10 collapse of XB "populations", groups of XBs featuring XB-XB cooperative effects within a group. The XB-group could 11 be interpreted as the crossbridges in a single RU, as crossbridges probably interact only within a RU [4]. Alternatively, 12 groups could be interpreted as all RUs of separate actin filaments, if we were to assume that all crossbridges in the 13 actin-activation model interact with each other. Finally, populations could be purely functional units. 14 In a typical XB-group development, force is first generated when a "primary" crossbridge is formed as a myosin head 15 binds actin at a relatively slow rate, initiating a new group. "Secondary" crossbridges are then formed at a much faster 16 rate, which results in collapsing of groups at relatively slow rates. The simplest equation for the fraction of groups G XB 17 engaged in force generation that guarantees a mono-exponential shape for the rate of force redevelopment (Ktr) curve 18 assumes the form 19 157 5. Ovchinnikov S. Max-min representation of piecewise linear functions. Contributions to Algebra and Geometry.158 2002;43(1):297-302. 159 6. Janssen P, Hunter WC. Force, not sarcomere length, correlates with prolongation of isosarcometric contraction. 160 American Journal of Physiology-Heart and Circulatory Physiology. 1995;269(2):H676-H685. 161 7. Janssen PM, Stull LB, Marbán E. Myofilament properties comprise the rate-limiting step for cardiac relaxation at 162 body temperature in the rat. American Journal of Physiology-Heart and Circulatory Physiology.163 2002;282(2):H499-H507. 164 8. Milani-Nejad N, Canan BD, Elnakish MT, Davis JP, Chung JH, Fedorov V, et al. The Frank-Starling mechanism 165involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium.