Charest Joseph L, Jennings Jean M, King William P, Kowalczyk Andrew P, García Andrés J
George W Woodruff School of Mechanical Engineering, Atlanta, GA, USA.
J Invest Dermatol. 2009 Mar;129(3):564-72. doi: 10.1038/jid.2008.265. Epub 2008 Aug 28.
Cell-extracellular matrix (ECM) and cell-cell interactions regulate keratinocyte cell fate and differentiation. In the present analysis, we examined the differentiation of primary human keratinocytes cultured on micropatterned substrates that varied the extent of cell-cell contact while maintaining constant cell-ECM areas. Bowtie-shaped micropatterned areas (75-1600 microm(2)) were engineered to either permit or prevent cell-cell contact for pairs of adherent keratinocytes. Cell pairs with direct cell-cell contact exhibited enhanced expression of the differentiation markers involucrin and keratin 10 compared to cells with no cell-cell contact. In contrast, available cell-spreading area, as regulated by pattern size, did not alter keratinocyte involucrin expression. Disruption of E-cadherin binding by either antibody blocking or expression of a dominant-negative receptor diminished the ability of micropattern-regulated cell-cell contact to modulate involucrin expression. These results demonstrate that cadherin-mediated cell-cell contact regulates early keratinocyte differentiation independently from changes in cell shape.
细胞-细胞外基质（ECM）和细胞-细胞间相互作用调节角质形成细胞的细胞命运和分化。在本分析中，我们研究了在微图案化基质上培养的原代人角质形成细胞的分化情况，这些基质改变了细胞-细胞接触的程度，同时保持细胞-ECM面积恒定。设计了领结形微图案化区域（75-1600平方微米），以允许或阻止成对贴壁角质形成细胞之间的细胞-细胞接触。与没有细胞-细胞接触的细胞相比，具有直接细胞-细胞接触的细胞对表现出分化标志物兜甲蛋白和角蛋白10的表达增强。相反，由图案大小调节的可用细胞铺展面积并未改变角质形成细胞兜甲蛋白的表达。通过抗体阻断或显性负性受体的表达破坏E-钙黏蛋白结合，会削弱微图案调节的细胞-细胞接触调节兜甲蛋白表达的能力。这些结果表明，钙黏蛋白介导的细胞-细胞接触独立于细胞形状的变化来调节早期角质形成细胞的分化。
