Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.
Chaos. 2020 Jan;30(1):011104. doi: 10.1063/1.5140714.
Intracellular reactions are intrinsically stochastic. Nonetheless, cells can reliably respond to the changing environment by sensing their target molecules sensitively and specifically, even with the existence of abundant structurally-similar non-target molecules. The mechanism of how the cells can balance and achieve such different characteristics is not yet fully understood. In this work, we demonstrate that these characteristics can be attained by a ligand-induced stochastic cluster formation of receptors via the noise-induced symmetry breaking, in which the intrinsic stochasticity works to enhance sensitivity and specificity. We also show that the noise-induced cluster formation enables cells to detect the target ligand reliably by compensating the abundant non-target ligands in the environment. The proposed mechanism may lead to a deeper understanding of a biological function of the receptor clustering and provide an alternative candidate for the reliable ligand detection to the kinetic proofreading.
细胞内反应本质上是随机的。然而，细胞可以通过敏感和特异地感知其靶分子来可靠地响应不断变化的环境，即使存在大量结构相似的非靶分子也是如此。细胞如何平衡并实现这种不同特性的机制尚不完全清楚。在这项工作中，我们证明了通过噪声诱导的对称性破缺，配体诱导的受体随机簇形成可以实现这些特性，其中内在的随机性有助于提高灵敏度和特异性。我们还表明，噪声诱导的簇形成可以通过补偿环境中丰富的非靶配体来使细胞可靠地检测到靶配体。所提出的机制可能会深入了解受体聚类的生物学功能，并为可靠的配体检测提供动力学校验的替代候选方案。
