Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
In traditional cell biology, the "cytoplasm" is the filling substance in the large space enclosed by the plasma membrane and surrounding the cell nucleus. It includes all non-nuclear cell organelles plus all fluid surrounding these organelles. Every point inside the cell, except the nucleus, is considered part of the cytoplasm. The "cytosol" is the liquid that fills all of the cytoplasmic region, except for fluids filling the interior of the cell organelles. Finally, the term "intracellular fluid" refers to all of the fluid inside a cell -- the cytosol plus the fluid inside each organelle, including the nucleus. Internal hydrostatic pressure in the cytosol ranges from ~23 N/m2 in the human erythrocyte cell1452 up to ~1.6 x 105 N/m2 in Amoeba proteus.1453
Fulton941 points out that in an average protein crystal ~40% of crystal mass is solvent water -- half strongly absorbed by the protein in the hydration shell and half resembling bulk water in its properties. Protein crystals may range from 20-90% solvent, or 10-80% protein, by weight. Muscle cells are ~23% protein, red cells ~35%, and actively growing cells contain 17-26% protein by weight.938 Thus the cytosolic environment more closely resembles proteinaceous crystals than dilute solutions (e.g., <0.1% proteins).
Hydration water is not immobile water like ice, but it does have reduced mobility, different solvating characteristics, a higher heat capacity, and is generally more ordered than bulk water.1936 Water of hydration coats the macromolecular cell components such as carbohydrates, nucleic acids, and the proteins of membranes, and is required for enzyme activity. Mammalian cells can maintain glycolysis and normal respiration down to 60% dehydration, which suggests that in a typical cell the cytosol may consist of ~60% bulk water and ~40% water of hydration. Distribution of ordered water in the cell is a heterogeneous and dynamic process, possibly cytonavigationally useful. For instance, ~55% of the water of the vegetal pole region of the frog oocyte is bound water, with only ~25% bound near the animal pole cytoplasm and ~10% bound in the nucleus.1937
Minton1010 showed that the volume occupied by proteins affects the activity of the other proteins in solution by "crowding" them into a smaller volume where they have less freedom of movement, forcing them into compact configurations that would occur far less frequently in dilute solutions. These effects can produce 50-100-fold excesses in protein activity over the values predicted from dilute solutions. Crowding also reduces diffusion mobility -- 60%-70% of glycolytic enzymes are freely diffusing (30%-40% are immobilized on the matrix) in squid axoplasm that contains 2% protein by weight, but only 20% of cytoplasmic proteins are freely diffusing in oocyte cytoplasm that contains 30%-40% protein by weight.941 Crowding effects could be nonspecific and due simply to protein number density, or they could be specific and maintained by selection. McConkey1011 estimates that about half of the polypeptides in the cell may participate in specific associational structures. For instance, many enzymes exist in complexes that may involve a dozen or more proteins, potentially complicating required nanorobotic actions; according to the substrate channelling hypothesis, these complexes can help speed up reactions.
Even without these crowding effects, cells display localized biochemical gradients that are cytonavigationally significant. Specific molecules, organelles and physiological processes may be localized to defined zones within the cell. This regional cytoplasmic differentiation is regulated in part by cytosolic Ca++ ion and by H+ ion (pH) spatial gradients.1076,1077 As another example, the cytosol immediately surrounding the Golgi apparatus is compositionally distinct from the cytosol that closely encircles the cell nucleus.531 Active chemical processing taking place within most cellular organelles produces persistent concentration gradients that may be used by in cyto nanorobots to establish proximity to specific organelles. Microsecond-cycle chemical nanosensors (Section 4.2.1) can sample the local environment far faster than the typical time required for a molecule to diffuse a distance of ~1 micron, the mean separation between adjacent major organelles inside human cells. Taking cytoplasm absolute viscosity h ~ 6 x 10-3 kg/m-sec,362 then from Eqn. 3.1 the 1-micron diffusion time tdiffuse >> tmeas (~1 microsec) for small molecules like amino acids or glucose (tdiffuse ~ 5000 microsec) or for 100,000-dalton macromolecules measuring ~10 nm in diameter (tdiffuse ~ 130,000 microsec).
Control proteins such as the transcription factors that regulate gene expression are typically present in only ~300-3000 copies of each type per cell. More common cytosolic proteins may be present in numbers up to 106-107 copies of each type per cell.
Last updated on 20 February 2003