Active Cells, Biochemistry & Physiology Genetics & Molecular Biology

Measuring the Mechanical Properties of Chromosomes

In plain English

AI plain-English summary

Every time a cell divides, it must package two metres of DNA into compact, X-shaped chromosomes that can withstand the physical forces of being pulled apart. This project uses optical tweezers—focused laser beams that can trap and stretch microscopic objects—to measure exactly how stiff, elastic, and strong those chromosomes are. The problem is that while scientists know a lot about the chemical composition of chromosomes, they know very little about their mechanical properties. Without that knowledge, it is impossible to understand why chromosomes sometimes fail to separate correctly during cell division, a failure that can lead to cancer or developmental disorders. This is fundamental science. The immediate goal is to develop reliable protocols for isolating intact chromosomes and to use the C-trap optical tweezers system to measure force-extension curves. The researchers will then use CRISPR to delete specific scaffold proteins—condensins and topoisomerases—to see which ones give chromosomes their strength. If successful, this work will provide the first quantitative biophysical parameters for chromosome mechanics. That deeper understanding could eventually inform why chromosome segregation errors occur, but the research does not promise a direct application. Similar fundamental studies of cellular mechanics have, in the past, unexpectedly improved our understanding of how cancer cells become more deformable and invasive.

View original technical description
This DPhil project investigates the mechanical properties of mitotic chromosomes— specifically elasticity, stiffness, and tension—using high- precision optical tweezers. One primary goal is to develop and optimise protocols for isolating structurally intact chromosomes from cells, enabling quantitative mechanical studies. Comparative assessments of extraction methods will combine fluorescence microscopy and atomic force microscopy to evaluate protein localisation and surface topography. A key technical objective is to establish routine use of the C-trap optical tweezers system for manipulating chromosomes tethered via biotinylated telomeres. Force-extension measurements will yield critical biophysical parameters, advancing our understanding of chromosome architecture. Subsequent work will involve targeted degradation of key chromosomal scaffold proteins (e.g., condensins, topoisomerases) via CRISPR-Cas-engineered cell lines to dissect their contributions to mechanical integrity. This research will shed light on how chromosomes withstand and respond to mechanical forces during mitosis, with implications for genome organisation and chromosome segregation fidelity during cell division. Keywords: mitotic chromosomes, optical tweezers, chromosome mechanics, C-trap, chromosome isolation, condensins, topoisomerases, genome architecture, biophysics

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Researchers

Barbara Tyler (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Diamond professorial fellowship for imaging chromosomes by coherent X-ray diffraction
The role of non-histone proteins in chromosome structure and function during mitosis
A computational approach to understand kinetochore-mediated force generation by microtubules in chromosome segregation
Coupling optical tweezers with light microscopy to unravel the mechanical forces acting on cellular organelles
Biochemical and biophysical characterisation of human meiotic cohesin complexes

Original classification

PhD Studentship (Basic)

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