Thermal motions enable a particle to probe the optimal interaction state when binding to a cell membrane. However, especially on the scale of microseconds and nanometers, position and orientation fluctuations are difficult to observe with common measurement technologies. Here, we show that it is possible to detect single binding events of immunoglobulin-G-coated polystyrene beads, which are held in an optical trap near the cell membrane of a macrophage. Changes in the spatial and temporal thermal fluctuations of the particle were measured interferometrically, and no fluorophore labeling was required. We demonstrate both by Brownian dynamic simulations and by experiments that sequential stepwise increases in the force constant of the bond between a bead and a cell of typically 20 pN/μm are clearly detectable. In addition, this technique provides estimates about binding rates and diffusion constants of membrane receptors. The simple approach of thermal noise tracking points out new strategies in understanding interactions between cells and particles, which are relevant for a large variety of processes, including phagocytosis, drug delivery, and the effects of small microplastics and particulates on cells.

中文翻译：

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在没有荧光的情况下测量热波动颗粒与细胞膜的逐步结合

热运动使粒子能够在与细胞膜结合时探测最佳相互作用状态。然而，特别是在微秒和纳米尺度上，位置和方向的波动很难用普通的测量技术观察到。在这里，我们表明可以检测免疫球蛋白 G 包被的聚苯乙烯珠的单一结合事件，这些珠被保持在巨噬细胞细胞膜附近的光阱中。粒子的空间和时间热波动的变化是通过干涉测量来测量的，并且不需要荧光团标记。我们通过布朗动力学模拟和实验证明，珠子和细胞之间的键的力常数的连续逐步增加（通常为 20 pN/μm）是可以明显检测到的。此外，该技术提供了关于膜受体结合率和扩散常数的估计。热噪声跟踪的简单方法指出了理解细胞和颗粒之间相互作用的新策略，这些相互作用与多种过程相关，包括吞噬作用、药物输送以及小微塑料和颗粒对细胞的影响。