Department of Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.
Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, Würzburg, 97070, Germany.
J Cell Sci. 2021 Apr 15;134(8). doi: 10.1242/jcs.252221. Epub 2021 Apr 27.
The mechanisms underlying the cellular response to extracellular matrices (ECMs) that consist of multiple adhesive ligands are still poorly understood. Here, we address this topic by monitoring specific cellular responses to two different extracellular adhesion molecules - the main integrin ligand fibronectin and galectin-8, a lectin that binds β-galactoside residues - as well as to mixtures of the two proteins. Compared with cell spreading on fibronectin, cell spreading on galectin-8-coated substrates resulted in increased projected cell area, more-pronounced extension of filopodia and, yet, the inability to form focal adhesions and stress fibers. These differences can be partially reversed by experimental manipulations of small G-proteins of the Rho family and their downstream targets, such as formins, the Arp2/3 complex and Rho kinase. We also show that the physical adhesion of cells to galectin-8 was stronger than adhesion to fibronectin. Notably, galectin-8 and fibronectin differently regulate cell spreading and focal adhesion formation, yet act synergistically to upregulate the number and length of filopodia. The physiological significance of the coherent cellular response to a molecularly complex matrix is discussed. This article has an associated First Person interview with the first author of the paper.
细胞对外界细胞外基质（ECM）的反应机制仍然知之甚少，而 ECM 由多种黏附配体组成。在这里，我们通过监测细胞对两种不同的细胞外黏附分子——主要整合素配体纤维连接蛋白和半乳糖凝集素-8（一种结合β-半乳糖苷残基的凝集素）以及两者混合物的特定细胞反应来解决这个问题。与细胞在纤维连接蛋白上的铺展相比，细胞在半乳糖凝集素-8 涂层底物上的铺展导致细胞的投影面积增加，丝状伪足的延伸更加明显，但无法形成焦点粘附和应力纤维。这些差异可以通过实验操纵 Rho 家族的小 G 蛋白及其下游靶标（如形成蛋白、Arp2/3 复合物和 Rho 激酶）部分逆转。我们还表明，细胞与半乳糖凝集素-8 的物理黏附强于与纤维连接蛋白的黏附。值得注意的是，半乳糖凝集素-8 和纤维连接蛋白以不同的方式调节细胞铺展和焦点粘附的形成，但协同作用以增加丝状伪足的数量和长度。讨论了细胞对分子复杂基质的一致反应的生理意义。本文有该论文第一作者的相关第一人称采访。
