Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1
Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1
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DOI：
10.1111/febs.15702
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发表时间：
2021-01-26
期刊：
影响因子：
5.4
通讯作者：
Weiss, Anthony S.
中科院分区：
文献类型：
--
作者：
Bochicchio, Brigida;Yeo, Giselle C.;Weiss, Anthony S.
弹性蛋白是一种细胞外基质成分，在弹性组织中具有重要的结构和生物学作用。驻留细胞和原弹性蛋白(弹性蛋白的单体)之间的相互作用支持弹性蛋白对细胞过程的调节。然而，原弹性蛋白-细胞相互作用的性质以及单个原弹性蛋白结构域对这些相互作用的贡献仅被部分阐明。在这项研究中，我们发现并鉴定了原弹性蛋白N端12和16区之间的新的细胞黏附位点。我们发现该区域与介导细胞附着和扩散的αV和α5β1整合素受体相互作用。该区域内的多肽序列跨越结构域14至中间结构域16，通过与多肽赖氨酸残基的静电作用与硫酸乙酰肝素结合，并诱导多肽的构象有序化。我们认为，结构域14-16通过细胞表面硫酸乙酰肝素糖胺聚糖直接最初的细胞附着，然后由αV和α5β1整合素促进的附着和扩散到原弹性蛋白的结构域12-16上。这些发现促进了我们对弹性蛋白基质生物学机制的理解，有可能增强弹性蛋白材料的组织再生结果。
Elastin is an extracellular matrix component with key structural and biological roles in elastic tissues. Interactions between resident cells and tropoelastin, the monomer of elastin, underpin elastin's regulation of cellular processes. However, the nature of tropoelastin-cell interactions and the contributions of individual tropoelastin domains to these interactions are only partly elucidated. In this study, we identified and characterized novel cell-adhesive sites in the tropoelastin N-terminal region between domains 12 and 16. We found that this region interacts with alpha V and alpha 5 beta 1 integrin receptors, which mediate cell attachment and spreading. A peptide sequence from within this region, spanning domains 14 to mid-domain 16, binds heparan sulfate through electrostatic interactions with peptide lysine residues and induces conformational ordering of the peptide. We propose that domains 14-16 direct initial cell attachment through cell-surface heparan sulfate glycosaminoglycans, followed by alpha V and alpha 5 beta 1 integrin-promoted attachment and spreading on domains 12-16 of tropoelastin. These findings advance our mechanistic understanding of elastin matrix biology, with the potential to enhance tissue regenerative outcomes of elastin-based materials.