Cytoplasmic Electric Fields and Electroosmosis: Possible Solution for the Paradoxes of the Intracellular Transport of Biomolecules

PLOS ONE, Dec 2019

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.

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Cytoplasmic Electric Fields and Electroosmosis: Possible Solution for the Paradoxes of the Intracellular Transport of Biomolecules

Citation: Andreev VP (2013) Cytoplasmic Electric Fields and Electroosmosis: Possible Solution for the Paradoxes of the Intracellular Transport of Biomolecules. PLoS ONE 8(4): e61884. doi:10.1371/journal.pone.0061884 Cytoplasmic Electric Fields and Electroosmosis: Possible Solution for the Paradoxes of the Intracellular Transport of Biomolecules Victor P. Andreev 0 William W. Lytton, SUNY Downstate MC, United States of America 0 1 Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida, United States of America, 2 Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America, 3 Center for Computational Sciences, University of Miami , Miami, Florida , United States of America 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. - 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 [12]. 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, however, ignores the fact that electric field and electric current do exist in a conductor connected to electric source, e.g. battery or a generator. Similarly, 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]. Importantly, when ion pump and/or ion channel activity is asymmetrically distributed over the plasma membrane, the cell may be able to drive ionic fluxes through itself and behaves as a miniature electrophoretic chamber [4]. This self electrophoresis principle was developed as early as 1966 [5], visualized in the meroistic ovary of an insect [6 8], further investigated and reviewed in [8,4]. 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]. The recent development of nanoparticles filled with the voltagesensitive fluorescent dye, allowed the direct measurement of the intracellular electric fields in the cytosolic and membrane regions of living cells (astrocytes) [9]. Importantly, strong electric fields (5?1053?106 V/m) were observed not only in the membrane and organelle regions but in the cytoplasm. The strongest electric fields were observed in the vicinity of mitochondria (inner mitochondrial membrane is known to have high electric potential of 2150 mV [1011]), however it was still quite strong (5?105 V/m) at the distance of several micrometers away from mitochondria [9]. The role of the cytoplasmic electric fields in the intracellular transport of proteins was investigated in two recent papers [12 13]. These papers argue that the transport of the messenger proteins from the cell (...truncated)


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Victor P. Andreev. Cytoplasmic Electric Fields and Electroosmosis: Possible Solution for the Paradoxes of the Intracellular Transport of Biomolecules, PLOS ONE, 2013, 4, DOI: 10.1371/journal.pone.0061884