Biophysical Reviews

, Volume 11, Issue 6, pp 851–872 | Cite as

Understanding biochemical processes in the presence of sub-diffusive behavior of biomolecules in solution and living cells

  • Sujit BasakEmail author
  • Sombuddha Sengupta
  • Krishnananda Chattopadhyay


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.


Anomalous diffusion Macromolecular crowding Protein stability Conformational equilibria Protein–protein interaction Biological functions Gene expression 



We would like to thank members of Krish lab for their critical inputs and their help. KC thanks CSIR for the funding.

Compliance with ethical standards

Conflict of interest

Sujit Basak declares that he has no conflict of interest. Sombuddha Sengupta declares that he has no conflict of interest. Krishnananda Chattopadhyay declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Biochemistry and Molecular PharmacologyUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Protein Folding and Dynamics Lab, Structural Biology and Bioinformatics, CSIR-Indian Institute of Chemical Biology (CSIR-IICB)KolkataIndia

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