Basak Sujit, Sengupta Sombuddha, Chattopadhyay Krishnananda
Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Protein Folding and Dynamics Lab, Structural Biology and Bioinformatics, CSIR-Indian Institute of Chemical Biology (CSIR-IICB), 4 Raja S.C Mullick Road, Jadavpur, Kolkata, West Bengal, 700032, India.
Biophys Rev. 2019 Dec;11(6):851-872. doi: 10.1007/s12551-019-00580-9. Epub 2019 Aug 23.
In order to maintain cellular function, biomolecules like protein, DNA, and RNAs have to diffuse to the target spaces within the cell. Changes in the cytosolic microenvironment or in the nucleus during the fulfillment of these cellular processes affect their mobility, folding, and stability thereby impacting the transient or stable interactions with their adjacent neighbors in the organized and dynamic cellular interior. Using classical Brownian motion to elucidate the diffusion behavior of these biomolecules is hard considering their complex nature. The understanding of biomolecular diffusion inside cells still remains elusive due to the lack of a proper model that can be extrapolated to these cases. In this review, we have comprehensively addressed the progresses in this field, laying emphasis on the different aspects of anomalous diffusion in the different biochemical reactions in cell interior. These experiment-based models help to explain the diffusion behavior of biomolecules in the cytosolic and nuclear microenvironment. Moreover, since understanding of biochemical reactions within living cellular system is our main focus, we coupled the experimental observations with the concept of sub-diffusion from in vitro to in vivo condition. We believe that the pairing between the understanding of complex behavior and structure-function paradigm of biological molecules would take us forward by one step in order to solve the puzzle around diseases caused by cellular dysfunction.
为了维持细胞功能,蛋白质、DNA和RNA等生物分子必须扩散到细胞内的目标空间。在这些细胞过程执行期间,胞质微环境或细胞核中的变化会影响它们的移动性、折叠和稳定性,从而影响它们在有组织且动态的细胞内部与相邻分子的瞬时或稳定相互作用。考虑到这些生物分子的复杂性质,用经典布朗运动来阐明它们的扩散行为是困难的。由于缺乏一个能够外推到这些情况的合适模型,对细胞内生物分子扩散的理解仍然难以捉摸。在这篇综述中,我们全面阐述了该领域的进展,重点关注细胞内不同生化反应中反常扩散的不同方面。这些基于实验的模型有助于解释生物分子在胞质和核微环境中的扩散行为。此外,由于我们主要关注的是对活细胞系统内生化反应的理解, 我们将实验观察结果与从体外到体内条件下的亚扩散概念相结合。我们相信,对生物分子复杂行为和结构-功能范式的理解之间的结合,将使我们向前迈进一步,以解决围绕细胞功能障碍引起的疾病的谜团。