On the formation and crystallization of sickle hemoglobin macrofibers

Abstract

We have characterized new aspects of macrofiber structure and assembly which provide a mechanism for macrofiber formation from fibers. After the formation of fibers, HbS forms macrofibers by the association of small, organized bundles of partially fused fibers. These macrofibers consist of double strands, packed into antiparallel rows, and are identical to double strands found in crystalline HbS, except that the double strands in macrofibers are axially displaced from their crystalline position and are twisted about the particle axis, whereas in crystals they are linear. In lateral views, electron micrographs of macrofibers show prominent sets of "rows." We use the number of these rows to designate a particular type of macrofiber. In this study we present micrographs of macrofibers with 3 to 11 rows visible in lateral views. Such particles contain from 20 to 200 double strands. The pitch of a macrofiber is coupled to the number of rows in a manner so that the angle between the molecules in the outermost double strand is always 1.8 degrees. This observation has led us to propose that the factor limiting the extent of lateral growth of macrofibers is distortions in bonding between the hemoglobin molecules in the outermost double strands. Similar considerations have provided an explanation of the factors that limit the lateral growth of fibers. Finally, we propose a simple mechanism for the formation of macrofibers from fibers. This mechanism postulates that integral numbers of fibers form specific types of macrofibers and has the virtue of conserving the polarity of the fibers.