Acidic pH is Required for the Multilamellar Assembly of Skin Barrier Lipids in Vitro

Lipid membrane remodeling belongs to the most fundamental processes in the body. The skin barrier lipids, which are ceramide-dominant and highly rigid, must attain an unusual multilamellar nanostructure with long periodicity to restrict water loss and prevent the entry of potentially harmful environmental factors. Our data suggest that the skin “acid mantle”, apart from regulating enzyme activities and keeping away pathogens, may also be a prerequisite for the multilamellar assembly of the skin barrier lipids. Atomic force microscopy on monolayers composed of synthetic or human SC lipids showed multilayer formation (ca 10 nm step height) in an acidic but not neutral environment. X-ray diffraction, Fourier-transform infrared spectroscopy, and permeability studies showed markedly altered lipid nanostructure and increased water loss at neutral compared to acidic pH. These findings are consistent with the altered organization of skin lipids and increased transepidermal water loss in conditions with inadequate skin acidification, e.g., in neonates, elderly, and patients with atopic dermatitis.

脂质膜重塑是人体最基本的过程之一。皮肤屏障脂质，以神经酰胺为主，具有高度刚性，必须形成一种非同寻常的多层纳米结构，具有长周期性，以限制水分流失并防止潜在有害环境因素的进入。我们的数据表明，除了调节酶活性和抵御病原体之外，皮肤‘酸性外膜’还可能是皮肤屏障脂质多层组装的先决条件。使用合成或人源表皮脂质单层构成的原子力显微镜研究表明，在酸性而非中性环境中，可观察到多层结构（约10纳米的层高）。X射线衍射、傅里叶变换红外光谱和渗透性研究显示，与酸性pH值相比，在中性pH值下，脂质纳米结构发生显著改变，水分流失增加。这些发现与皮肤脂质组织改变和皮肤屏障功能不足条件下的经皮水分流失增加相一致，例如新生儿、老年人和特应性皮炎患者。