The role of liquid-crystalline (mesophase) structures in extra-cellular morphogenesis is widely recognised. This paper explores the role of intra-cellular mesophases, formed from intermediate filaments in a concerted process of unit-length-filament (ULF) polymerisation and phase separation, in controlling cortical cell differentiation and morphology of animal hairs.
Structural evidence from the extant literature for the development of anisotropic phases, initially as classic dispersed tactoids, is presented, along with key parallels with other macromolecular systems. Important results from the statistical thermodynamic theory of phase separation by semi-rigid rods are invoked to explain various features of early-stage structure development. Intermediate filament protein head groups appear to have a crucial role in stabilising the mesophase by configurational and mixing entropy, competing with factors such as polydispersity, to control the concentration difference between phases, which is quasi-static during phase co-existence. A long-ignored model for self-assembly, proposed by P J Flory and coworkers in 1978, based on a concerted process of equilibrium polymerisation and phase separation, is invoked to account for the observed short filaments in the tactoidal phase.
Cell differentiation is correlated with different mesophase textures, either nematic or double-twist, and with varying degrees of anisotropic phase coalescence, arising from differences in mesogen orientation and length in apposed tactoids. That a double-twist structure will be the preferred mesophase for short, flexible, intermediate filaments, is rationalised by a combination of mesophase and mesogen mechanics. The model thus explains features of mature structures such as the fibril-matrix ratios in different cell types. The rapidity of trichocyte IF formation suggests that a sudden-transition equilibrium polymerisation, involving a high-energy initiating species, obeying the same statistical model as several other biological transitions, may be involved. This leads to an appealing symmetry, with the key factor in both polymerisation and mesophase stability being the retention of protein head-group entropy.