Koslover Elena F, Spakowitz Andrew J
Biophysics Program, Stanford University, Stanford, California 94305, USA.
Phys Rev E Stat Nonlin Soft Matter Phys. 2012 Jul;86(1 Pt 1):011906. doi: 10.1103/PhysRevE.86.011906. Epub 2012 Jul 10.
A wide array of biological processes occur at rates that vary significantly with force. Instantaneous molecular forces fluctuate due to thermal noise and active processes, leading to concomitant fluctuations in biomolecular rate constants. We demonstrate that such fluctuations have a dramatic effect on the transition kinetics of force-dependent processes. As an illustrative, biologically relevant example, we model the pausing of eukaryotic RNA polymerase as it transcribes nucleosomal DNA. Incorporating force fluctuations in the model yields qualitatively different predictions for the pausing time scales when compared to behavior under the average force alone. We use our model to illustrate the broad range of behaviors that can arise in biomolecular processes that are susceptible to force fluctuations. The fluctuation time scale, which varies significantly for in vivo biomolecular processes, yields very different results for overall rates and dramatically alters the force regime of relevance to the transition. Our results emphasize the importance of transient high-force behavior for determining kinetics in the fluctuating environment of a living cell.
大量生物过程的发生速率会随力的变化而显著不同。瞬时分子力会因热噪声和主动过程而波动，导致生物分子速率常数随之波动。我们证明，这种波动对力依赖过程的转变动力学有显著影响。作为一个具有生物学相关性的示例，我们对真核RNA聚合酶转录核小体DNA时的暂停进行建模。与仅考虑平均力时的行为相比，在模型中纳入力的波动会对暂停时间尺度产生定性不同的预测。我们用模型来说明在易受力波动影响的生物分子过程中可能出现的广泛行为。波动时间尺度在体内生物分子过程中差异很大，会对整体速率产生截然不同的结果，并极大地改变与转变相关的力的范围。我们的结果强调了瞬时高力行为对于确定活细胞波动环境中动力学的重要性。
