Karagöz Zeynep, Rijns Laura, Dankers Patricia Y W, van Griensven Martijn, Carlier Aurélie
Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, the Netherlands.
Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, the Netherlands.
Comput Struct Biotechnol J. 2020 Dec 29;19:303-314. doi: 10.1016/j.csbj.2020.12.025. eCollection 2021.
The interactions between cells and their extracellular matrix (ECM) are critically important for homeostatic control of cell growth, proliferation, differentiation and apoptosis. Transmembrane integrin molecules facilitate the communication between ECM and the cell. Since the characterization of integrins in the late 1980s, there has been great advancement in understanding the function of integrins at different subcellular levels. However, the versatility in molecular pathways integrins are involved in, the high diversity in their interaction partners both outside and inside the cell as well as on the cell membrane and the short lifetime of events happening at the cell-ECM interface make it difficult to elucidate all the details regarding integrin function experimentally. To overcome the experimental challenges and advance the understanding of integrin biology, computational modeling tools have been used extensively. In this review, we summarize the computational models of integrin signaling while we explain the function of integrins at three main subcellular levels (outside the cell, cell membrane, cytosol). We also discuss how these computational modeling efforts can be helpful in other disciplines such as biomaterial design. As such, this review is a didactic modeling summary for biomaterial researchers interested in complementing their experimental work with computational tools or for seasoned computational scientists that would like to advance current integrin models.
细胞与其细胞外基质（ECM）之间的相互作用对于细胞生长、增殖、分化和凋亡的稳态控制至关重要。跨膜整合素分子促进了ECM与细胞之间的通讯。自20世纪80年代末整合素被鉴定以来，在不同亚细胞水平上对整合素功能的理解有了很大进展。然而，整合素所涉及的分子途径具有多样性，其在细胞内外以及细胞膜上的相互作用伙伴高度多样，并且细胞-ECM界面发生的事件持续时间较短，这使得通过实验阐明整合素功能的所有细节变得困难。为了克服实验挑战并推进对整合素生物学的理解，计算建模工具已被广泛使用。在本综述中，我们总结了整合素信号传导的计算模型，同时解释了整合素在三个主要亚细胞水平（细胞外、细胞膜、细胞质）的功能。我们还讨论了这些计算建模工作如何有助于生物材料设计等其他学科。因此，本综述是一份教学性的建模总结，面向有兴趣用计算工具补充其实验工作的生物材料研究人员，或希望改进当前整合素模型的经验丰富的计算科学家。
