Relating Self-assembly to Spatio-temporal Keratin Expression in the Wool Follicle

Abstract

Two of the present authors have presented a model for macrofibril template self-assembly which is based on a concerted process of sudden, delayed, short filament formation with immediate phase transfer to a lyotropic liquid crystal (mesophase). In recent years, information on the spatio-temporal patterns of keratin protein expression within wool follicles has come to hand, and we here report some recently acquired important information in this area. If the "mesophase model" is to remain credible it must be compatible with the spatio-temporal patterns of keratin expression. This paper explores the match between the mesophase model and patterns of protein expression, and concludes that they are broadly consistent. At present the model does not extend to keratin associated protein (KAP) expression. The model is also particularly successful in explaining macrofibril structural features in different cell types.

De novo filament formation by human hair keratins K85 and K35 follows a filament development pattern distinct from cytokeratin filament networks

“…As an explanation of proto‐MF formation in cortical cells, a mesophase (lyotropic liquid crystal) separation model has been proposed from detailed TEM data and thermodynamic theories [26,34,35]. In this model, the abundant hair keratin pair, K85 and K31, builds up a high concentration of ULFs in the lower cortex cells, and any further lengthening of the ULFs into short IFs will quickly result in the formation of a concentrated oriented phase, the mesophase, appearing initially as spindle‐shaped tactoids, i.e., early‐stage proto‐MFs.…”

“…In the cortex of a hair or wool fiber, hair keratin IFs are arrayed into bundles, in which each IF is surrounded by a matrix material composed of keratinassociated proteins (KAPs) [3,4,[24][25][26]. The supramolecular structures organized by hair keratin IF bundles and KAPs, termed macrofibrils (MFs), have a diameter of 200-500 nm and a maximum length of ~10 µm and fill the cortex by lateral and longitudinal assembly along the fiber [4,17,[25][26][27][28][29][30][31][32][33][34][35][36][37]. Transmission electron microscopy (TEM) studies of MF formation have revealed the appearance of hair keratin IF bundles in the lower cortex, i.e., proto-macrofibril (proto-MFs) with a width of 50-100 nm and a length of several hundred nanometers, some of which are attached to a desmosome, while others are isolated in the cytoplasm [4,26,28,30,31,34,35,37].…”

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“…Nuclear DNA is degraded as cells move away from the bulb . Early observations have recently been validated using modern microscopy methods, which, along with live cell imaging of bulb cortical cells, suggests nuclear degradation begins well before the top of the DP.…”

“…Cortical keratins appear in the cytoplasm beginning at Auber's line (first K35, and K85, and then K31) . Keratin structures first appear a few cell lengths distal of the onset of K31 expression . These first structures are dense aggregations of intermediate filaments (IFs) and can be associated with desmosomes or be cytoplasmic .…”

“…Keratin structures first appear a few cell lengths distal of the onset of K31 expression . These first structures are dense aggregations of intermediate filaments (IFs) and can be associated with desmosomes or be cytoplasmic . How these aggregations form, and why no loose filament network forms (as seen in the root sheath) is probably due to cortex‐specific keratin‐keratin interactions .…”