Center for RNA Biomedicine, Single Molecule Analysis Group, Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109-1055, USA.
Bioessays. 2019 Aug;41(8):e1800244. doi: 10.1002/bies.201800244. Epub 2019 Jun 27.
Biology arises from the crowded molecular environment of the cell, rendering it a challenge to understand biological pathways based on the reductionist, low-concentration in vitro conditions generally employed for mechanistic studies. Recent evidence suggests that low-affinity interactions between cellular biopolymers abound, with still poorly defined effects on the complex interaction networks that lead to the emergent properties and plasticity of life. Mass-action considerations are used here to underscore that the sheer number of weak interactions expected from the complex mixture of cellular components significantly shapes biological pathway specificity. In particular, on-pathway-i.e., "functional"-become those interactions thermodynamically and kinetically stable enough to survive the incessant onslaught of the many off-pathway ("nonfunctional") interactions. Consequently, to better understand the molecular biology of the cell a further paradigm shift is needed toward mechanistic experimental and computational approaches that probe intracellular diversity and complexity more directly. Also see the video abstract here https://youtu.be/T19X_zYaBzg.
生物学源于细胞中拥挤的分子环境，这使得根据通常用于机制研究的简化、低浓度的体外条件来理解生物学途径成为一项挑战。最近的证据表明，细胞生物聚合物之间存在低亲和力相互作用，但其对导致生命涌现特性和可塑性的复杂相互作用网络的影响仍定义不明确。这里使用质量作用考虑来强调，从细胞成分的复杂混合物中预期的大量弱相互作用显著影响生物途径的特异性。具体来说，在途径上，即“功能上”的相互作用是那些热力学和动力学上足够稳定的相互作用，足以在许多非途径（“非功能”）相互作用的不断冲击下存活下来。因此，为了更好地理解细胞的分子生物学，需要向更直接地探测细胞内多样性和复杂性的机制实验和计算方法进行进一步的范式转变。也可在此处查看视频摘要 https://youtu.be/T19X_zYaBzg。
