How would you describe the shape of the isometric force-length-activity relation (FLAR) of striated muscle sarcomeres to your students? Simple textbook knowledge, right? At very long lengths, the sarcomere (and thus the whole fiber) is unable to exert any active force even when fully activated. When the sarcomere is gradually held at shorter lengths, the force increases somewhat linearly. For a certain 'optimal' length -- or 'plateau' region -- the force output reaches its maximum, before it decreases again for even shorter lengths.

When it comes to explaining this shape, the long-length characteristic (the descending branch) is commonly associated with the relative overlap between thin and thick filaments. However, explanations for the force decrease at shorter lengths (the ascending branch) are rather vague. In the literature, there exist several attempts of explaining a piece-wise linear ascending branch by assuming (i) repelling forces between opposing thin filaments, (ii) thick filament compression at the Z-disk, or (iii) steric hindrance of cross-bridge building. This talk addresses these hypotheses by revealing sources, misconceptions, and counterevidence. Further, a biophysical model is presented, exploiting know mechanisms such as the volume constancy of the filament lattice, electrostatics-induced cross-bridge building, and Hill's equation of ligand-receptor complexes. A combination of these mechanisms fully explains the experimentally observed FLAR and even pertains to submaximally Calcium-activated fibers -- a realm where conventional approaches struggle.