Evans E, Ritchie K
Department of Physics, University of British Columbia, Vancouver, Canada.
Biophys J. 1997 Apr;72(4):1541-55. doi: 10.1016/S0006-3495(97)78802-7.
In biology, molecular linkages at, within, and beneath cell interfaces arise mainly from weak noncovalent interactions. These bonds will fail under any level of pulling force if held for sufficient time. Thus, when tested with ultrasensitive force probes, we expect cohesive material strength and strength of adhesion at interfaces to be time- and loading rate-dependent properties. To examine what can be learned from measurements of bond strength, we have extended Kramers' theory for reaction kinetics in liquids to bond dissociation under force and tested the predictions by smart Monte Carlo (Brownian dynamics) simulations of bond rupture. By definition, bond strength is the force that produces the most frequent failure in repeated tests of breakage, i.e., the peak in the distribution of rupture forces. As verified by the simulations, theory shows that bond strength progresses through three dynamic regimes of loading rate. First, bond strength emerges at a critical rate of loading (> or = 0) at which spontaneous dissociation is just frequent enough to keep the distribution peak at zero force. In the slow-loading regime immediately above the critical rate, strength grows as a weak power of loading rate and reflects initial coupling of force to the bonding potential. At higher rates, there is crossover to a fast regime in which strength continues to increase as the logarithm of the loading rate over many decades independent of the type of attraction. Finally, at ultrafast loading rates approaching the domain of molecular dynamics simulations, the bonding potential is quickly overwhelmed by the rapidly increasing force, so that only naked frictional drag on the structure remains to retard separation. Hence, to expose the energy landscape that governs bond strength, molecular adhesion forces must be examined over an enormous span of time scales. However, a significant gap exists between the time domain of force measurements in the laboratory and the extremely fast scale of molecular motions. Using results from a simulation of biotin-avidin bonds (Izrailev, S., S. Stepaniants, M. Balsera, Y. Oono, and K. Schulten. 1997. Molecular dynamics study of unbinding of the avidin-biotin complex. Biophys. J., this issue), we describe how Brownian dynamics can help bridge the gap between molecular dynamics and probe tests.
在生物学中，细胞界面处、内部及下方的分子连接主要源于弱非共价相互作用。如果保持足够长的时间，这些键在任何拉力水平下都会断裂。因此，当用超灵敏力探针进行测试时，我们预计内聚材料强度和界面处的粘附强度是与时间和加载速率相关的特性。为了研究从键强度测量中能学到什么，我们将克拉默斯液体反应动力学理论扩展到受力时的键解离，并通过键断裂的智能蒙特卡罗（布朗动力学）模拟来检验这些预测。根据定义，键强度是在重复断裂测试中产生最频繁失效的力，即断裂力分布中的峰值。如模拟所验证，理论表明键强度在加载速率的三个动态区域中变化。首先，键强度在临界加载速率（≥0）时出现，此时自发解离频率刚好足以使分布峰值保持在零力。在略高于临界速率的慢加载区域，强度随加载速率的微弱幂次增长，反映了力与键合势的初始耦合。在更高的速率下，会过渡到快速区域，其中强度在几十年内随着加载速率的对数持续增加，与吸引力类型无关。最后，在接近分子动力学模拟范围的超快加载速率下，键合势迅速被快速增加的力压倒，以至于结构上仅存在纯粹的摩擦阻力来阻碍分离。因此，为了揭示控制键强度的能量图景，必须在极大的时间尺度范围内研究分子粘附力。然而，实验室中力测量的时域与分子运动的极快尺度之间存在显著差距。利用生物素 - 抗生物素蛋白键模拟的结果（伊兹拉列夫，S.，S. 斯捷潘尼扬茨，M. 巴尔塞拉，Y. 大野，和 K. 舒尔滕。1997 年。抗生物素蛋白 - 生物素复合物解离的分子动力学研究。《生物物理杂志》，本期），我们描述了布朗动力学如何有助于弥合分子动力学与探针测试之间的差距。
