The self-assembly of keratin intermediate filaments into macrofibrils: Is this process mediated by a mesophase?

A concerted polymerization-mesophase separation model for formation of trichocyte intermediate filaments and macrofibril templates. 1: Relating phase separation to structural development

“…During later development within the follicle these proto-macrofibrillar structures (here called macrofibril templates) formed in the cytoplasm are infiltrated with associated proteins (IFAPs), which, during subsequent keratinisation, are covalently bonded to one another and to the IFs, and dehydrated to form the finished macrofibrils as observed in the cortex of mammalian hairs. It was postulated (McKinnon, 2006) that prior to IFAP in-fill and keratinisation the mesophase is stabilised at a given rod-rod separation by the conformational entropy of the pendant intermediate-filament protein head groups (which have some properties peculiar to this class of IF proteins) though it cannot be ruled out that IF tails may also contribute in such a role.…”

“…One of the authors has previously presented a basic theory (McKinnon, 2006) that macrofibril formation within the cortex cells (trichocytes) of developing animal fibres comes about initially through separation of an intracellular mesophase created from highly anisometric (rod-like) intermediate filaments (IFs) in the cytoplasm. During later development within the follicle these proto-macrofibrillar structures (here called macrofibril templates) formed in the cytoplasm are infiltrated with associated proteins (IFAPs), which, during subsequent keratinisation, are covalently bonded to one another and to the IFs, and dehydrated to form the finished macrofibrils as observed in the cortex of mammalian hairs.…”

<i>In vitro</i> Assembly Properties of Human Type I and II Hair Keratins

“…The molecular mechanism inducing the formation of these three types of MFs has not yet been clarified (Fraser et al, 2003;McKinnon, 2006;McKinnon and Harland, 2011). Differences in both the composition and content of KAPs in the three types of MFs suggest that they play an important role in determining the precise mode of MF packing (Fujikawa et al, 2011;Matsunaga et al, 2013;Plowman et al, 2007;Rogers et al, 2006).…”

“…In TEM and electron tomographic studies of hair fiber and wool, three types of MFs with different IF arrangements have been identified (para, ortho, and meso), and their distribution across a fiber appear to relate to the crimp or waviness of a fiber (Bryson et al, 2009;Jones and Pope, 1985;Marshall et al, 1991;McKinnon, 2006;McKinnon and Harland, 2011;Morioka, 2009;Orwin, 1979). The molecular mechanism inducing the formation of these three types of MFs has not yet been clarified (Fraser et al, 2003;McKinnon, 2006;McKinnon and Harland, 2011).…”

“…Some TEM images of the cross-sections of early proto-MFs showed that distinctly separated IFs are arranged on a hexagonal basal lattice like a columnar hexagonal liquid crystal, with no matrix proteins interpolated between the filaments (McKinnon, 2006). Proto-MFs coalesce with each other into MFs that are around 400 nm wide and several micrometers long in the mid-to upper cortex (Jones and Pope, 1985;McKinnon, 2006;McKinnon and Harland, 2011;Orwin, 1979). It is more efficient to form proto-MFs composed of short IFs and then connect them longitudinally Assembly of Hair Keratins and laterally into MFs than to bundle long IFs into MFs.…”