Titin and the sarcomere symmetry paradox

Titin is thought to play a major role in myofibril assembly, elasticity and stability. A single molecule spans half the sarcomere and makes interactio ns with both a thick filament and the Z-line. In the unit cell structure of each half sarcomere there is one thick filament with 3-fold symmetry and t wo thin filaments with approximately 2-fold symmetry. The minimum number of titin molecules that could satisfy both these symmetries is 12. We determi ned the actual number of titin molecules in a unit cell from scanning trans mission electron microscopy mass measurements of end-filaments. One of thes e emerges from each tip of the thick filament and is thought to be the in-r egister aggregate of the titin molecules associated with the filament. The mass per unit length of the end-filament (17.1 kDa/nm) is consistent with s ix titin molecules not 12. Thus the number of titin molecules present is in sufficient to satisfy both symmetries. We suggest a novel solution to this paradox in which four of the six titin molecules interact with the two thin filaments in the unit cell, while the remaining two interact with the two thin filaments that enter the unit cell from the adjacent sarcomere. This a rrangement would augment mechanical stability in the sarcomere. (C) 2001 Ac ademic Press.