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A numerical mechanical model integrating actin treadmilling and receptor recycling to explain selective disengagement of immune cells.
Mathematical Biosciences ( IF 1.9 ) Pub Date : 2019-08-23 , DOI: 10.1016/j.mbs.2019.108244
Myles Kim 1
Affiliation  

T-killer cells of the immune system eliminate virus-infected cells by releasing toxic granules through a direct cell to cell surface interface (synapse). The release of toxic granules only through the cell surface interface assures the specificity of the immune response. The toxic granule releasing apparatus, however, may not be aligned toward the synapse at the moment of the synapse formation. Therefore, mechanisms for reorienting the killing apparatus inside the T-killer cell to the interface with the target is required. Numerous research works were reported to suggest the mechanisms with direct and indirect evidence, but the most adversary situation, that is when the cell's initial orientation is the complete opposite of the desired direction, either remained answered or brought skepticism toward the suggested mechanisms. To address this issue, a computational mechanical model of T-killer cell synapse formation is constructed to test previously suggested models in a more realistic setting and at the same time to test previously neglected component in the model, namely the actin network formation on the synapse. In this model, by capturing the mechanical interaction between T-killer cell surface receptor dynamics and mechanical properties of synapse formation, it is shown that T-killer cells can selectively engage or disengage from the target cell depending on the killing apparatus alignment with the target. The mechanism works as a safeguard measure ensuring target-cell killing and specificity, so it will be effective when T-killer cells are stranded in situations where the alignment of the killing apparatus is challenging.

中文翻译:

整合肌动蛋白跑步机和受体循环的数字力学模型来解释免疫细胞的选择性脱离。

免疫系统的T杀伤细胞通过直接细胞与细胞表面的界面(突触)释放有毒颗粒,从而消除了被病毒感染的细胞。仅通过细胞表面界面释放有毒颗粒可确保免疫反应的特异性。但是,有毒颗粒释放装置在突触形成的瞬间可能未对准突触。因此,需要用于将T-杀伤细胞内的杀伤装置重新定向至与靶的界面的机构。据报道,许多研究工作提出了具有直接和间接证据的机制,但最不利的情况是,当细胞的初始方向与所需方向完全相反时,要么仍然被回答,要么对所建议的机制持怀疑态度。为了解决这个问题,构建了T杀伤细胞突触形成的计算力学模型,以在更现实的环境中测试先前建议的模型,同时测试模型中先前被忽略的组件,即突触上的肌动蛋白网络形成。在该模型中,通过捕获T杀伤细胞表面受体动力学与突触形成的机械性质之间的机械相互作用,表明T杀伤细胞可以根据杀伤设备与靶标的对准情况选择性地与靶细胞接合或脱离。 。该机制是确保靶细胞杀伤和特异性的一种安全措施,因此在杀伤装置的排列面临挑战的情况下将T杀伤细胞搁浅时,该机制将非常有效。构建T-杀伤细胞突触形成的计算力学模型,以在更现实的环境中测试先前建议的模型,同时测试模型中先前被忽略的组件,即突触上肌动蛋白网络的形成。在该模型中,通过捕获T杀伤细胞表面受体动力学与突触形成的机械性质之间的机械相互作用,表明T杀伤细胞可以根据杀伤设备与靶标的对准情况选择性地与靶细胞接合或脱离。 。该机制是确保靶细胞杀伤和特异性的一种安全措施,因此在杀伤装置的排列面临挑战的情况下将T杀伤细胞搁浅时,该机制将非常有效。构建T-杀伤细胞突触形成的计算力学模型,以在更现实的环境中测试先前建议的模型,同时测试模型中先前被忽略的组件,即突触上肌动蛋白网络的形成。在该模型中,通过捕获T杀伤细胞表面受体动力学与突触形成的机械性质之间的机械相互作用,表明T杀伤细胞可以根据杀伤设备与靶标的对准情况选择性地与靶细胞接合或脱离。 。该机制可作为确保靶细胞杀伤和特异性的保障措施,因此,在杀伤装置对准困难的情况下,将T杀伤细胞搁浅时,该机制将非常有效。
更新日期:2019-11-01
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