Transient Anomalous Diffusion of Telomeres in the Nucleus of Mammalian Cells

Abstract

We measured individual trajectories of fluorescently labeled telomeres in the nucleus of eukaryotic cells in the time range of 10 À2 -10 4 sec by combining a few acquisition methods. At short times the motion is subdiffusive with hr 2 i $ t and it changes to normal diffusion at longer times. The short times diffusion may be explained by the reptation model and the transient diffusion is consistent with a model of telomeres that are subject to a local binding mechanism with a wide but finite distribution of waiting times. These findings have important biological implications with respect to the genome organization in the nucleus. DOI: 10.1103/PhysRevLett.103.018102 PACS numbers: 87.16.Zg, 05.40.Jc, 87.15.Vv The nucleus of the eukaryotic cell contains tens of thousands of genes ($23 000 in human) organized as chromosomal DNA. This crowded environment contains packed genetic material, RNA transcripts, protein factors, and a variety of nuclear bodies. The genetic information (DNA) can be either replicated to form daughter cells, or transcribed to RNA molecules leading to protein translation. These processes depend on the ability of protein factors to locate and interact with specific DNA sequence within this packed nucleus [1], as well as on the organization and structure of chromatin in the nucleus [2]. Telomeres are the end caps of the linear eukaryotic chromosomes. They play an important role in maintaining chromosome organization and integrity throughout the cell cycle. The telomeres are protected by a number of protein factors that are collectively referred to as shelterin and can bind to either the nuclear envelope, nuclear matrix, or heterochromatin, depending on the cell species [3]. Therefore, studying the dynamics of telomeres can shed light on chromosome dynamics, the role of telomeres in genome organization, and the coordination of physical structures and biological processes in the nucleus [4].Chromosomes occupy specific nuclear volumes referred to as chromosome territories [5], and their motion is highly constrained. The diffusion of telomeres was previously studied on a limited time scale of either minutes [6] or 1-200 sec [7] and exhibited mainly normal constrained diffusion with a heterogeneous diffusion coefficient of 2-6 Â 10 À4 m 2 =s. This is significantly lower than the diffusion of small molecules such as dextran in the nucleus (10-100 m 2 =s), which reflects the dense nature of the nucleus. The dynamics of other nuclear bodies as well as messenger RNAs were also measured [8][9][10] and anomalous diffusion was found for specific DNA loci [11].In this study, we examined the diffusion properties of telomeres in the nucleus in a broad time range of almost 6 orders of magnitude (10 À2 -10 4 sec ). Such a broad time range was employed by combining two different imaging setups on the same microscope. We find that the diffusion is anomalous at short times of $10 À2 -10 3 sec . It changes to normal diffusion at longer time intervals and the diffusion constants are found to have a wide distribution...

Persistent super-diffusive motion of Escherichia coli chromosomal loci

“…This behaviour is characterized by a robust scaling law for the mean-square displacement of a locus, specifically a power law in time with exponent aC0.4, consistent across many experimental conditions and chromosomal positions [4][5][6] . Similar scaling laws have been found for chromosomal loci in eukaryotes such as yeast 7 and humans 8 . Notably, the power law exponent B0.4 is not reproduced by standard polymer models 6 .…”

Simulation of diffusion in a crowded environment

“…15,16 Experimental studies concerning the motion of proteins and lipids in cells were performed using uorescence correlation spectroscopy, [17][18][19][20] pulsed eld gradient NMR 21 and single particle tracking (SPT). 6,7,[22][23][24][25][26][27] In many cases an anomalous diffusion was detected, i.e. the mean square displacement of objects hDr 2 i scaled with time t as hDr 2 i $ t a , with a < 1.…”

Transient subdiffusion from an Ising environment

“…We will show that requiring the existence of a minimal energy scale (as occurs out of criticality) implies that subdiffusion can appear only as a transient behavior, while at longer times the particle experiences normal diffusion. Transient subdiffusion can have different manifestations [19] and/or appear in very different contexts [20][21][22][23][24][25]. In [19], the total motion of telomeres in the nucleus of mammal cells shows transient subdiffusion, which the authors relate to the reptation model.…”

“…Transient subdiffusion can have different manifestations [19] and/or appear in very different contexts [20][21][22][23][24][25]. In [19], the total motion of telomeres in the nucleus of mammal cells shows transient subdiffusion, which the authors relate to the reptation model. In [20,21], the behavior of diffusion as a function of the temperature is explained in certain glasses by modeling them as dynamical environments giving raise to transient subdiffusion.…”