Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Biophys J. 2011 Mar 16;100(6):1463-72. doi: 10.1016/j.bpj.2011.01.064.
The diffusion of receptors within the two-dimensional environment of the plasma membrane is a complex process. Although certain components diffuse according to a random walk model (Brownian diffusion), an overwhelming body of work has found that membrane diffusion is nonideal (anomalous diffusion). One of the most powerful methods for studying membrane diffusion is single particle tracking (SPT), which records the trajectory of a label attached to a membrane component of interest. One of the outstanding problems in SPT is the analysis of data to identify the presence of heterogeneity. We have adapted a first-passage time (FPT) algorithm, originally developed for the interpretation of animal movement, for the analysis of SPT data. We discuss the general application of the FPT analysis to molecular diffusion, and use simulations to test the method against data containing known regions of confinement. We conclude that FPT can be used to identify the presence and size of confinement within trajectories of the receptor LFA-1, and these results are consistent with previous reports on the size of LFA-1 clusters. The analysis of trajectory data for cell surface receptors by FPT provides a robust method to determine the presence and size of confined regions of diffusion.
质膜二维环境中受体的扩散是一个复杂的过程。虽然某些成分是根据随机漫步模型（布朗扩散）扩散的，但大量研究发现膜扩散是非理想的（异常扩散）。研究膜扩散最有力的方法之一是单粒子跟踪（SPT），它记录了与感兴趣的膜成分相连的标记的轨迹。SPT 中的一个突出问题是分析数据以识别异质性的存在。我们改编了最初为解释动物运动而开发的首次通过时间（FPT）算法，用于分析 SPT 数据。我们讨论了 FPT 分析在分子扩散中的一般应用，并使用模拟数据测试了该方法对包含已知限制区域的数据的有效性。我们得出的结论是，FPT 可用于识别轨迹中限制的存在和大小LFA-1 的受体，这些结果与之前关于 LFA-1 簇大小的报告一致。通过 FPT 对细胞表面受体的轨迹数据进行分析，提供了一种确定扩散受限区域的存在和大小的稳健方法。
