J. Cosmet. Sci., 61, 467–477 (November/December 2010) 467 The thickness of 18-MEA on an ultra-high-sulfur protein surface by molecular modeling UPENDRA NATARAJAN and CLARENCE ROBBINS, Molecular Modeling & Simulation Lab, Department of Chemical Engineering, Indian Institute of Technology, Madras, Chennai 600036, India (U.N.), and 12425 Lake Ridge Circle, Clermont, FL, 34711 (C.R.). Accepted for publication August 31, 2010. Synopsis The use of computational chemistry techniques via molecular modeling software provides additional support to the hair surface model by Negri et al. (1) and refi nes the thickness of the 18-methyl eicosanoic acid (18- MEA) lipid layer attached by thioester linkages to an ultra-high-sulfur protein (UHSP) at 1.08 ± 0.2 nm. This value compares favorably to the thickness of that same layer from X-ray photoelectron spectroscopy (XPS) measurements by Ward et al. (2) at 1.00 ± 0.5 nm on Soxhlet-extracted wool. The model clarifi es that the results of Ward et al. via XPS are not an artifact of high vacuum (3), but due to relaxation of the 18-MEA structure onto the wool protein backbone as suggested by Zahn et al. (4). In this molecular model, 18-MEA is attached to beta sheets of an UHSP via thioester linkages as suggested by Negri et al. in their 1993 study (15) and by earlier work by Evans et al. (5). The beta sheets of this model provide an intersheet spacing of 0.7 nm and a beta sheet density of 1.42 g/cm3compared with Allworden membrane fractions that varied from 1.39 to 1.54 g/cm3 (6). INTRODUCTION It is of utmost practical importance to cosmetic science that we understand the true “vir- gin” surface of hair fi bers so that we can determine changes to that surface by cosmetic treatments and be able to reconstruct that surface. This paper is part of an attempt to help clarify the actual structure of the virgin hair fi ber surface. The surface of mammalian hairs is covered with a thin covalently bound lipid layer of 18-MEA that is bonded to a proteinaceous cell membrane called epicuticle (1,7) (see Figure 1). Negri et al. (1) have shown that the outer surface of hair fi bers consists of about 75% of a heavily cross-linked protein and about 25% of a fatty acid that is pre- dominantly 18-MEA. These scientists have proposed a model wherein the fatty acid layer (attached lipid layer) is connected to the underlying fi brous protein layer through thioester linkages involving the cysteine residues of the underlying epicuticle proteins (1,4) (see Figure 1). These scientists concluded that the attachment of 18-MEA is through thioester linkages because chlorine water would not remove this lipid layer if

JOURNAL OF COSMETIC SCIENCE 468 it were attached through an ester or amide linkage however, chlorine water will readily cleave thioester bonds. Jones and Rivett (7) have stated that secondary ion mass spectrometry (SIMS) and XPS “indicate the surface of wool fi bers is almost exclusively hydrocarbon” consisting of 18- MEA and free lipids (solvent-extractable lipids), as described later in this paper. The protein membrane (epicuticle) is approximately 13-nm thick (8). Since the attachment of 18-methyl eicosanoic acid to keratin fi bers is through thioester linkages and the cell membrane protein is cross-linked through cysteine linkages, the 18-MEA must be attached to a UHSP (1). Concerns have been expressed in the literature (3,4) about the actual thickness of the 18-MEA layer, based on the fact that Ward et al. (2) used XPS to estimate the thickness of this surface lipid layer at 1.0 ± 0.5 nm, but this estimate is less than half of the length of a fully stretched 18-MEA molecule as calculated by Jones and Rivett (7). Zahn et al. (4) suggested that the difference could be explained by 18-MEA folding back on itself and onto the wool surface, while Peet et al. (3) sug- gested that the measurement by Ward et al. was likely an artifact created by the high vacuum conditions of XPS. To resolve these issues about the thickness of 18-MEA attached by thioester linkages to a UHSP surface and to test the Negri et al. model and learn more about the keratin fi ber surface, we employed molecular modeling software to construct and test a skeleton model (Figure 1) of 18-MEA attached by thioester linkages to beta sheets of a keratin- associated protein-5 (KAP-5) from a family of UHSP proteins found in the cuticle of keratin fi bers. Figure 1. Schematic representation of the beta sheets setup for the keratin fi ber surface molecular model.