整合素和细胞黏附的多尺度模型。
Multiscale models of integrins and cellular adhesions.
机构信息
Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA; Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA. Electronic address: https://twitter.com/davidodde.
出版信息
Curr Opin Struct Biol. 2023 Jun;80:102576. doi: 10.1016/j.sbi.2023.102576. Epub 2023 Mar 20.
Computational models of integrin-based adhesion complexes have revealed important insights into the mechanisms by which cells establish connections with their external environment. However, how changes in conformation and function of individual adhesion proteins regulate the dynamics of whole adhesion complexes remains largely elusive. This is because of the large separation in time and length scales between the dynamics of individual adhesion proteins (nanoseconds and nanometers) and the emergent dynamics of the whole adhesion complex (seconds and micrometers), and the limitations of molecular simulation approaches in extracting accurate free energies, conformational transitions, reaction mechanisms, and kinetic rates, that can inform mechanisms at the larger scales. In this review, we discuss models of integrin-based adhesion complexes and highlight their main findings regarding: (i) the conformational transitions of integrins at the molecular and macromolecular scales and (ii) the molecular clutch mechanism at the mesoscale. Lastly, we present unanswered questions in the field of modeling adhesions and propose new ideas for future exciting modeling opportunities.
基于整合素的黏附复合物的计算模型揭示了细胞与外部环境建立连接的机制的重要见解。然而，单个黏附蛋白构象和功能的变化如何调节整个黏附复合物的动力学仍然很大程度上难以捉摸。这是因为单个黏附蛋白的动力学（纳秒和纳米）与整个黏附复合物的涌现动力学（秒和微米）之间存在时间和长度尺度上的巨大分离，以及分子模拟方法在提取准确的自由能、构象转变、反应机制和动力学速率方面的限制，这些方法可以为更大规模的机制提供信息。在这篇综述中，我们讨论了基于整合素的黏附复合物的模型，并强调了它们在以下方面的主要发现：（i）整合素在分子和大分子尺度上的构象转变，以及（ii）介观尺度上的分子离合器机制。最后，我们提出了黏附建模领域的未解决问题，并为未来令人兴奋的建模机会提出了新的想法。
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