The human stratum corneum as extended, covalently cross-linked biopolymer: mathematics, molecules, and medicine.

A novel mathematical and molecular hypothesis is proposed to account for the peculiar organization of human epidermis. Mathematically, the organization of the interfollicular epidermis is hypothesized to be a tetratomic identity manifesting a gravitational logic in the arrangement of its functional compartments. The squares of the natural numbers; i.e., 1, 4, 9, and 16 are taken, on empirical grounds, to correspond to the number of cell layers in the respective epidermal strata (germinativum, spinosum, granulosum, and corneum). The outer two strata, overlying the Langerhans cells, constitute the 'living' and 'dead' components of the traditional 'epidermal barrier'. Together, these two strata illustrate in their union of 9 + 16 = 25 cells, a way of conceiving the skin surface (the body-environment identity) as both closure and contact. The organization of human epidermis into functional units based on phi, the golden section ratio, builds upon this gravitational logic. Finally, the fact that the extensively cross-linked proteolipid envelope of the cornified epidermal cell is a single multi-gene molecule is deemed scientifically incontrovertible. The molecular hypothesis in need of validation and verification is whether the corneodesmosomal 'rivets' linking one corneocyte to another are covalently bonded structures. If so, the cornified scaffolding of the stratum corneum constitutes a highly organized, extended, multi-gene, polymer molecule strategically located precisely at the shared surface of the body and environment. This hypothesis places the differentiated structure of the epidermis, an ectodermal derivative like the brain, front and center in the translation of molecular biology to clinical bedside care.