Cytoplasmic convection currents and intracellular temperature gradients

Author summary Individual cells are the building blocks of all living things, and a myriad of processes occur within their walls. To facilitate the generation of energy and manufacturing of proteins and other molecules critical for cell survival, work and growth, intracellular material often must be shuttled to different locations or compartments within the cell. It is vital that we understand this intracellular transport if we hope to fully understand cell functioning. Some mechanisms of intracellular transport are well established, including random diffusive motion and active transport by molecular motor proteins. Recently, experimental evidence has suggested there are areas of substantial local heating within the cell, introducing the possibility of temperature gradient-driven convective circulation. Here, we explore the theoretical possibility of such mechanisms competing with diffusion to drive intracellular flows, and identify the conditions necessary for this to occur. For intracellular material with low diffusivity and in the presence of temperature gradients described in the recent literature, simulations suggest this mode of intracellular transport may indeed feasible and should be further validated experimentally. Intracellular thermometry has recently demonstrated temperatures in the nucleus, mitochondria, and centrosome to be significantly higher than those of the cytoplasm and cell membrane. This local thermogenesis and the resulting temperature gradient could facilitate the development of persistent, self-organizing convection currents in the cytoplasm of large eukaryotes. Using 3-dimensional computational simulations of intracellular fluid motion, we quantify the convective velocities that could result from the temperature differences observed experimentally. Based on these velocities, we identify the conditions necessary for this temperature-driven bulk flow to dominate over random thermal diffusive motion at the scale of a single eukaryotic cell. With temperature gradients of the order 1 degrees C and diffusion coefficients comparable to those described in the literature, Peclet numbers >= 1 are feasible and permit comparable or greater effects of convection than diffusion in determining intracellular mass flux. In addition to the temperature gradient, the resulting flow patterns would also depend on the spatial localization of the heat source, the shape of the cell membrane, and the complex intracellular structure including the cytoskeleton. While this intracellular convection would be highly context-dependent, in certain settings, convective motion could provide a previously unrecognized mechanism for directed, bulk transport within eukaryotic cells.