Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan 17;432(2):621-631.
doi: 10.1016/j.jmb.2019.11.022. Epub 2019 Dec 20.

Physics and Biology (of Chromosomes)

John F Marko  1
Affiliations

Physics and Biology (of Chromosomes)

John F Marko. J Mol Biol. .

Abstract

Advances in molecular biology, optics, genetics, and bioinformatics have opened the door to mapping, in molecular detail, processes inside living cells. With the ability to observe the individual moving parts of cellular machinery, concepts formerly confined to physics are entering mainstream biology. This article discusses a few ideas of this sort related to chromosome biology, to illustrate what kinds of insights physics might yet bring to our understanding of living systems.

Keywords: chromatin; chromosomes; phase separation; polymer biophysics; quantitative biology.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
A. The triad of quantities with different units that characterize a simple machine: length, time and force. B. Thermal fluctuations drive random-walk diffusive motions of molecules, the basis of all molecular motion inside cells: a diffusive trajectory of a Dendra2 molecule in a cell is shown (bar 500 nm, time between data points 10 ms) [12]. C. Molecular motors use chemical energy (e.g., ATP) to make molecules move processively in one direction: observations of the motion of an individual myosin V molecule are shown [13]. D. Images of human U2OS cells crawling in a culture dish [14], field of view approximately 60 μm, time between frames approximately 30 minutes.
Figure 2.
Figure 2.
A. Optical observation of phase separation of synthetic polymer liquids in two dimensions: as in all bulk phase separation processes the domains or “bubbles” of the separating phases grown indefinitely in size [18] (all bars 100 μm). B. If two polymers with the tendency to separate are chemically bonded together (sketch) to make a diblock copolymer, they can undergo microphase formation to form layers (left) [21], or other more exotic structures such as the bicontinuous network (right) where regions shaped locally like the “tetrapod” sketched to right self-organize [22]. C. Nucleoli in Xenopus oocytes take the form of many small droplets (bar 100 μm) which can be observed to undergo fusion and flow (lower panels, smaller droplets approximately 20 μm diameter) similar to coalescence during phase separation [23]. D. Nucleoli in human cells (red in upper panels, bar 5 μm) have been observed to undergo shape changes in time similar to that of small liquid droplets (upper right panels: the fluctuations are small, refer to the original paper for details); fusion events also have been observed (lower panels, bar 2 μm) [24].
Figure 3.
Figure 3.
A. Viscoelastic object in cell (e.g., cytoskeleton, chromosome) jiggling, undergoing length and width changes in time which can be analyzed to obtain frequency-dependent storage G′ and loss G″ moduli. B. Moduli for cytoskeletal material (actin non-covalently crosslinked by an actin-crosslinking protein) studied in vitro. Filled squares indicate G′ while open squares indicate G″; note dips in G″ (arrows) [34]. C. Sketch of moduli of “soft glassy” materials similar to those of B [36], which under white-noise drive can show a viscoelastic peak, due to the dip in G″ (reminiscent in shape to a resonance but of entirely different physical origin; figure adapted from Ref. [36]).
Figure 4.
Figure 4.
Bacterial chromosome inside [43](A, bar 2 μm), and outside (B, bar 2 μm) [42] a cell. Tightly confining DNA, as inside these two bacterial cells, means confining not just the polymer segments (C) but the many counterions per segment (D), with a resulting large counterion pressure.
Figure 5.
Figure 5.
A. Images of chromosomes in rapidly growing and dividing E. coli bacterial cells where replicated chromosomes are thought to separate themselves from one another without the aid of cytoskeletal structures. Bar is 2 μm. B. Eukaryote cell cycle metaphase chromosome compaction process. (images are of newt N. viridescens cells, bar is 20 μm [46]). C. Lengthwise compaction. As polymers (chromosomes) are lengthwise compacted (made shorter and thicker by local folding), under conditions where topology can change (if topoisomerases are present and active), entanglements will be progressively removed at larger and larger length scales. D. Loop extrusion hypothesis for lengthwise compaction. Loop-extruding machines (LEMs) bind and actively generate loops (left); if they dissociate slowly, they will self-organize a long polymer into an array of loops robustly anchored by multiple LEMs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. National Research Council. BIO2010: Transforming Undergraduate Education for Future Research Biologists. Washington, DC: The National Academies Press; 2003. - PubMed
    1. Davis CA, Hitz BC, Sloan CA, Chan ET, Davidson JM, Gabdank I, et al. The Encyclopedia of DNA elements (ENCODE): data portal update. Nucleic acids research. 2018;46:D794–D801. - PMC - PubMed
    1. Kerpedjiev P, Abdennur N, Lekschas F, McCallum C, Dinkla K, Strobelt H, et al. HiGlass: web-based visual exploration and analysis of genome interaction maps. Genome Biol. 2018;19:125. - PMC - PubMed
    1. Eagen KP. Principles of Chromosome Architecture Revealed by Hi-C. Trends Biochem Sci. 2018;43:469–78. - PMC - PubMed
    1. Clouter WG, Powell LS. The M.K.S. system. The Vocational Aspect of Secondary and Further Education. 1952;4:71–81.

Publication types

LinkOut - more resources