Resonant waveguide grating biosensor for living cell sensing
Resonant waveguide grating biosensor for living cell sensing
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DOI：
10.1529/biophysj.105.077818
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Balakrishnan, Jitendra
中科院分区：
文献类型：
--
作者：
Fang, Ye;Ferrie, Ann M.;Balakrishnan, Jitendra
本文提出了理论分析和实验数据的使用谐振波导光栅（RWG）生物传感器来表征刺激介导的细胞反应，包括信号。该生物传感器能够检测细胞内容物在垂直和平行于传感器表面的两个方向上的再分布。这种能力依赖于在线监测具有多个光学输出参数的细胞响应，包括入射角的变化和谐振峰的形状。尽管峰形的变化主要归因于平行于传感器表面的刺激调制的细胞内容物的不均匀再分布，但入射角的变化主要反映了垂直于传感器表面的刺激触发的动态质量再分布（DMR）。获得的光学特征，并用于表征几个细胞过程，包括细胞粘附和扩散，脱离和信号通过胰蛋白酶消化，并通过表皮生长因子受体或缓激肽B2受体的信号。建立了一个数学模型，将缓激肽介导的DMR信号与B2受体信号循环中细胞内蛋白质的动态迁移和受体内化联系起来。该模型采用一组非线性常微分方程的形式，描述了B2受体的四种不同状态、蛋白质和受体-蛋白质复合物的扩散以及DMR响应的变化。经典的分析表明，该系统收敛到一个独特的光学签名，其动力学（振幅，过渡时间和动力学）是依赖于缓激肽信号输入，并与使用RWG生物传感器观察到的一致。本研究为用RWG生物传感器探测活细胞提供了基础，通常，光学生物传感器。
This article presents theoretical analysis and experimental data for the use of resonant waveguide grating (RWG) biosensors to characterize stimulation-mediated cell responses including signaling. The biosensor is capable of detecting redistribution of cellular contents in both directions that are perpendicular and parallel to the sensor surface. This capability relies on online monitoring cell responses with multiple optical output parameters, including the changes in incident angle and the shape of the resonant peaks. Although the changes in peak shape are mainly contributed to stimulation-modulated inhomogeneous redistribution of cellular contents parallel to the sensor surface, the shift in incident angle primarily reflects the stimulation-triggered dynamic mass redistribution (DMR) perpendicular to the sensor surface. The optical signatures are obtained and used to characterize several cellular processes including cell adhesion and spreading, detachment and signaling by trypsinization, and signaling through either epidermal growth factor receptor or bradykinin B2 receptor. A mathematical model is developed to link the bradykinin-mediated DMR signals to the dynamic relocation of intracellular proteins and the receptor internalization during B2 receptor signaling cycle. This model takes the form of a set of nonlinear, ordinary differential equations that describe the changes in four different states of B2 receptors, diffusion of proteins and receptor-protein complexes, and the DMR responses. Classical analysis shows that the system converges to a unique optical signature, whose dynamics ( amplitudes, transition time, and kinetics) is dependent on the bradykinin signal input, and consistent with those observed using the RWG biosensors. This study provides fundamentals for probing living cells with the RWG biosensors, in general, optical biosensors.