Abstract
The objective of the paper is to show that electroosmotic flow might play an important role in the intracellular transport of biomolecules. The paper presents two mathematical models describing the role of electroosmosis in the transport of the negatively charged messenger proteins to the negatively charged nucleus and in the recovery of the fluorescence after photobleaching. The parameters of the models were derived from the extensive review of the literature data. Computer simulations were performed within the COMSOL 4.2a software environment. The first model demonstrated that the presence of electroosmosis might intensify the flux of messenger proteins to the nucleus and allow the efficient transport of the negatively charged phosphorylated messenger proteins against the electrostatic repulsion of the negatively charged nucleus. The second model revealed that the presence of the electroosmotic flow made the time of fluorescence recovery dependent on the position of the bleaching spot relative to cellular membrane. The magnitude of the electroosmotic flow effect was shown to be quite substantial, i.e. increasing the flux of the messengers onto the nucleus up to 4-fold relative to pure diffusion and resulting in the up to 3-fold change in the values of fluorescence recovery time, and therefore the apparent diffusion coefficient determined from the fluorescence recovery after photobleaching experiments. Based on the results of the modeling and on the universal nature of the electroosmotic flow, the potential wider implications of electroosmotic flow in the intracellular and extracellular biological processes are discussed. Both models are available for download at ModelDB.
Highlights
The majority of the studies of the intracellular electric fields discuss the role of membrane potential and electric fields across cellular and nuclear membranes as reviewed in [1,2]
We suggest that electroosmotic flow can influence the motion of proteins during the fluorescence recovery after photobleaching (FRAP) experiments and might contribute to the values of apparent diffusion coefficients measured in these experiments
Transport of Messenger Proteins to the Nucleus Here we present the results of the axisymmetric model of the transport of negatively charged messenger proteins in the polarized cell, which is modeled as a cylinder (10 mm radius, and 10 mm height)
Summary
The majority of the studies of the intracellular electric fields discuss the role of membrane potential and electric fields across cellular and nuclear membranes as reviewed in [1,2]. The electric field in the cytoplasm is usually ignored based on the reasoning that ‘‘high ionic strength and electrical conductibility of physiological media do not allow a significant electric field to be sustained at distances greater than 1 nm (the Debye length) from the originating charge distribution’’ [1] This reasoning, ignores the fact that electric field and electric current do exist in a conductor connected to electric source, e.g. battery or a generator. The biological cell is an active device which generates ion gradients with the help of ion pumps (carrier protein coupled to a source of metabolic energy such as ATP hydrolysis) These ion gradients allow the passive transport of ions through the ion channels of the cellular membrane [3]. The plethora of possible cytoplasmic electric field and electric current configurations were discussed, depending on the distribution of ion pumps and ion channels, position of nucleus (in or out of main transcytoplasmic flux) and type of nuclear envelope [4]
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