© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999

8.5.4.4 Nucleoplasm and Chromatin

The nucleoplasm is the semifluid matrix in the interior of the nucleus. It contains some condensed but mostly extended chromatin (called heterochromatin and euchromatin, respectively), as well as a structural nuclear matrix of nonchromatin (mostly protein) material (Section 8.5.4.6). The chromatin represents chromosomes as they exist between cell divisions. Chromosomes assume a highly condensed (compact) state as the cell prepares to divide, but after mitosis most of the chromosomes relax into a highly extended state. The nucleus of the human cell contains 46 chromosomes of varying lengths, in 23 pairs. Each of these in turn are composed principally of a single deoxyribonucleic acid (DNA) molecule. The DNA contains the genes of the cell, and all ~100,000 genes are represented, though not expressed, in each nucleated cell. The nucleosol, or fluid component of the nucleoplasm, contains salts, nutrients, and other needed biochemicals. A number of different granules are also present.⁹³⁸

During interphase (e.g., between cell divisions), individual chromosomes occupy compact, discrete territories within the nucleus that may range up to 4 microns in diameter (Fig. 8.47).^{2464-2467,3410-3417} The structure and location of these territories is specific for both cell type and mitotic stage,^3412,3413 and may be arranged in the same spatial order as is found in the wheel-shaped ring aggregate known as the chromosome rosette at the time of mitotic prometaphase.¹⁰⁶⁰ It has been proposed that active genes are preferentially localized to the periphery of the chromosome territories; RNA templates would be preferentially produced at the surfaces of these territories and then shed into interchromosomal domain channels for further processing and transport.¹⁵²⁹ Others have argued against this.³⁴¹⁴ But knowledge of any such spatial orderings, which was woefully incomplete in 1998, might permit intranuclear nanorobots to approximate their position inside the nucleus once the locations of three or more specific chomosomes have been definitively established. The diameter of a territory D_territory ~ D_nucleus (c_chromosome / c_genome)^1/3 ~ 3 microns, where c_chromosome is chromosome size and c_genome is genome size, both measured in base pairs, and D_nucleus is the diameter of the nucleus.²⁴⁶⁴

Note, however, that these territories are not rigid. Changes in the relative positions of chromosomal territories often occur at ~0.3-0.4 nm/sec, and intraterritorial movement and flexing of subchromosomal foci measuring 400-800 nm in diameter have also been observed.^1529,3415 Both cytoplasm and nucleoplasm may contain numerous as yet undiscovered intricate substructures that could provide many new navigational aids. An important task for early nanomedicine-oriented research will be to fully explore and elucidate this fine structure, and to determine whether or not it is stable enough to be relied upon in any way for intracellular navigation.

In its most relaxed state, chromatin resembles a network of bumpy threads weaving their way through the nucleoplasm. Chromatin is composed of roughly equal amounts of negatively charged DNA (comprising the chromosomes) and globular histone proteins (basic proteins which carry a positive charge at the normal pH found in the cell).⁹³⁸ Nucleosomes, the fundamental units of chromatin, are spherical clusters of eight histone proteins, connected like beads on a string by a DNA molecule that winds around each of them. The average cell nucleus contains 25 million nucleosomes, also called histone octamers. Each nucleosome is encircled by 146 base pairs of DNA. Nucleosomes have a mass of 206,000 daltons. About half of nucleosome mass is protein and half is DNA. Each human chromosome contains DNA with an average contour length of ~75 mm. (See Chapter 20 for more details.)

Last updated on 20 February 2003