Nonthermal fluctuations accelerate biomolecular motors

Abstract

Intracellular transport is essential for maintaining cellular function. This process is driven by different mechanisms in prokaryotic and eukaryotic cells. In small prokaryotic cells, diffusion is the primary means of transport, while larger eukaryotic cells also rely on active transport by molecular motors such as kinesin and dynein. Recently, it has become evident that, in addition to diffusion based on thermal fluctuations (Brownian motion), which was conventionally considered a diffusion mechanism within living cells, nonthermal fluctuations generated by metabolic activities play a crucial role in intracellular diffusion. Similarly, while molecular motors have been proposed to exploit thermal fluctuations in the environment following the direct observation and manipulation of single molecules, they have also been reported to utilize nonthermal fluctuations in recent years. This review begins with a brief overview of the historical knowledge of diffusive intracellular transport, which has been extended from the thermal fluctuations to the nonthermal fluctuations generated by metabolic activity. It then introduces recent findings on how nonthermal fluctuations accelerate the motion of molecular motors and discusses future perspectives on the general effects of these fluctuations on molecules in living cells.

Keywords: Kinesin; Molecular motor; Nonthermal fluctuations; Optical tweezers; Single molecule manipulation.

Fig. 1

Thermal and nonthermal fluctuations. a Microparticles in water move in a random manner, pushed by the thermal motion of water molecules even at equilibrium conditions. b Inside living cells, the cytosol is actively agitated by the consumption of chemical free energy derived from metabolic activity

Fig. 2

Kinesin and optical tweezers. a Molecular motor kinesin transports intracellular vesicles. b Schematic of the optical tweezers measurement system. Feedback control of the laser focus enables the application of arbitrary external forces to the walking kinesin via a probe particle

Fig. 3

Acceleration of kinesin due to external force fluctuations. a Experimental results. b Numerical simulations using a mathematical model. c Numerical simulations with physiologically plausible external force fluctuations. d Acceleration phenomena with nonthermal fluctuations in living cells. Reprinted figures with permission from (Ariga et al. 2021). Copyright (2024) by the American Physical Society