A Supramolecular Polymerization Approach to the Growth of the Myofibril

Abstract

Extended linear structures self-assemble by the multi-stage-open-association mechanism of supramolecular polymerization (MSOA). Application of the model requires the identification of a repeating unit, the main-chain supramolecular bond, and the binding constant. The strength of the bond and the degree of polymerization become extremely large when multiple sites for non-covalent interactions occur. These expectations had been previously verified in the case of the neuronal axon, for which the above parameters were assessed from its known molecular structure. The more complex case of the myofibril is analyzed here. The specific interactions that connect neighboring sarcomers have been a matter of debate. Recent work has focused on the bond between titin and α-actinin localized at the terminal Z-zones of each sarcomer. Elaboration of literature data suggests that titin-α-actinin interactions do bridge neighboring sarcomers, promoting the polymerization of myofibrils that attain macroscopic dimensions consistently with the MSOA predictions. The rationale for the complex structuration of single sarcomers is discussed.

Supramolecular and Liquid Crystalline Contributions to the Assembly of Myofibril

“…The following short summary underlines the fundamental theoretical concepts of chemical and shape recognition processes. The detailed concepts allowed the recent prediction of the equilibrium structure of the myofibril [3,4].…”

“…Refined quantitative analyses are needed to assess the extent of all contributions to the dynamic functioning of the myofiber. The process may also be described in the context of the Complexity paradigm [4].…”

“…In recent communications, we analyzed the structure and the contraction mechanism of the myofibril. We highlighted the basic physico-chemical principles likely involved in both the assembling and the functioning of the sarcomere [3,4]. In particular, the interdigitated distribution of thick and thin filaments in the contracted state was suggested to reflect a memory of a liquid crystalline order of mixtures of the two unrestricted components in the presence of an excess of Ca 2+ ions.…”

“…For instance, the self-assembling mechanism of the basic repeating unit of the myofibril (the sarcomer, see Figure 1), remained obscure during over a half century of investigations on striated muscles. A complex model for muscle contraction based on ATP-dependent interactions between actin and the motor myosin filament remained unchallenged, in spite of relevant advances in the area of fundamental self-assembling mechanisms [1][2][3][4].…”

“…The linear organization of the sarcomeric components along the fiber axis was attributed to a series of chemical Molecules 2020, 25, 862 2 of 7 cross-linkages engineered by Nature to optimize the mechanical function of the muscle. The driving step in the assembly of the myofibril was postulated to be the supramolecular polymerization of the sarcomers [4]. In the present communication, we compare the assembly steps predicted by our model with steps documented by direct analyses of the myofibrillogenesis process and the structure of mature myofibris [5][6][7][8][9].…”