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Computational estimation of chemical reaction rates in extracellular vesicle signaling
Nano Communication Networks ( IF 2.9 ) Pub Date : 2023-04-24 , DOI: 10.1016/j.nancom.2023.100455
Martin Damrath , Mohammad Zoofaghari , Milica Lekić , Hamid Khoshfekr Rudsari , Fabrizio Pappalardo , Mladen Veletić , Ilangko Balasingham

The rates of chemical reactions involved in cell-to-cell communication can serve as a powerful tool for advanced theranostics and in establishing a molecular communication link between bio-transceivers. Reaction rates are usually experimentally measured by quantifying chemical products, which is challenging when several signal transduction mechanisms are involved in the signaling pathway. Without loss of generality, we focus on extracellular vesicle (EV) cell-to-cell signaling and propose a computational method to estimate the chemical reaction rates which characterize a process by which EVs are taken by cells. The method is based on measuring only the time-course of environmental EVs, and eliminates the need to measure either bound or internalized EVs which is usually essential for experimental evaluation of the rates by using advanced molecular imaging modalities. As an alternative to a proposed approximation by a linear system model, our computation exploits a nonlinear system model in which the impact of limited receptor sites on the recipient cell membrane is incorporated. The reaction rates are obtained through a suggested linear and iterative approach as well as a novel way of applying Michaelis–Menten kinetics in the frequency domain. The range of validity of each technique is evaluated by varying the number of free binding sites on the cell membrane in relation to the initial number of environmental EVs. In conclusion, the proposed methods are very effective in assessing the dynamics of the EV uptake using a simple in vitro platform.



中文翻译:

细胞外囊泡信号传导中化学反应速率的计算估计

细胞间通讯中涉及的化学反应速率可以作为高级治疗诊断学和在生物收发器之间建立分子通讯链接的有力工具。反应速率通常通过量化化学产物进行实验测量,当信号通路中涉及多种信号转导机制时,这是具有挑战性的。在不失一般性的情况下,我们专注于细胞外囊泡 (EV) 细胞间信号传导,并提出了一种计算方法来估计化学反应速率,化学反应速率表征了 EV 被细胞吸收的过程。该方法基于仅测量环境电动汽车的时间进程,并消除了测量结合或内化 EV 的需要,这通常对于使用先进的分子成像模式对速率进行实验评估是必不可少的。作为线性系统模型所提出的近似的替代方案,我们的计算利用了非线性系统模型,其中结合了有限受体位点对受体细胞膜的影响。反应速率是通过建议的线性和迭代方法以及在频域中应用米氏动力学的新方法获得的。每种技术的有效性范围是通过改变细胞膜上与环境 EV 初始数量相关的自由结合位点的数量来评估的。总之,所提出的方法在使用简单的方法评估 EV 摄取的动态方面非常有效 作为线性系统模型所提出的近似的替代方案,我们的计算利用了非线性系统模型,其中结合了有限受体位点对受体细胞膜的影响。反应速率是通过建议的线性和迭代方法以及在频域中应用米氏动力学的新方法获得的。每种技术的有效性范围是通过改变细胞膜上与环境 EV 初始数量相关的自由结合位点的数量来评估的。总之,所提出的方法在使用简单的方法评估 EV 摄取的动态方面非常有效 作为线性系统模型所提出的近似的替代方案,我们的计算利用了非线性系统模型,其中结合了有限受体位点对受体细胞膜的影响。反应速率是通过建议的线性和迭代方法以及在频域中应用米氏动力学的新方法获得的。每种技术的有效性范围是通过改变细胞膜上与环境 EV 初始数量相关的自由结合位点的数量来评估的。总之,所提出的方法在使用简单的方法评估 EV 摄取的动态方面非常有效 反应速率是通过建议的线性和迭代方法以及在频域中应用米氏动力学的新方法获得的。每种技术的有效性范围是通过改变细胞膜上与环境 EV 初始数量相关的自由结合位点的数量来评估的。总之,所提出的方法在使用简单的方法评估 EV 摄取的动态方面非常有效 反应速率是通过建议的线性和迭代方法以及在频域中应用米氏动力学的新方法获得的。每种技术的有效性范围是通过改变细胞膜上与环境 EV 初始数量相关的自由结合位点的数量来评估的。总之,所提出的方法在使用简单的方法评估 EV 摄取的动态方面非常有效体外平台。

更新日期:2023-04-24
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