Latent analysis of unmodified biomolecules and their complexes in solution with attomole detection sensitivity
(2015) In Nature Chemistry 7(10). p.802-809- Abstract
- The study of biomolecular interactions is central to an understanding of function, malfunction and therapeutic modulation of biological systems, yet often involves a compromise between sensitivity and accuracy. Many conventional analytical steps and the procedures required to facilitate sensitive detection, such as the incorporation of chemical labels, are prone to perturb the complexes under observation. Here we present a 'latent' analysis approach that uses chemical and microfluidic tools to reveal, through highly sensitive detection of a labelled system, the behaviour of the physiologically relevant unlabelled system. We implement this strategy in a native microfluidic diffusional sizing platform, allowing us to achieve detection... (More)
- The study of biomolecular interactions is central to an understanding of function, malfunction and therapeutic modulation of biological systems, yet often involves a compromise between sensitivity and accuracy. Many conventional analytical steps and the procedures required to facilitate sensitive detection, such as the incorporation of chemical labels, are prone to perturb the complexes under observation. Here we present a 'latent' analysis approach that uses chemical and microfluidic tools to reveal, through highly sensitive detection of a labelled system, the behaviour of the physiologically relevant unlabelled system. We implement this strategy in a native microfluidic diffusional sizing platform, allowing us to achieve detection sensitivity at the attomole level, determine the hydrodynamic radii of biomolecules that vary by over three orders of magnitude in molecular weight, and study heterogeneous mixtures. We illustrate these key advantages by characterizing a complex of an antibody domain in the solution phase and under physiologically relevant conditions. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8058530
- author
- Yates, Emma V. ; Mueller, Thomas ; Rajah, Luke ; De Genst, Erwin J. ; Arosio, Paolo ; Linse, Sara LU ; Vendruscolo, Michele ; Dobson, Christopher M. and Knowles, Tuomas P. J.
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Chemistry
- volume
- 7
- issue
- 10
- pages
- 802 - 809
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:26391079
- wos:000361753200009
- scopus:84942314882
- ISSN
- 1755-4330
- DOI
- 10.1038/NCHEM.2344
- language
- English
- LU publication?
- yes
- id
- 95bed059-abfb-475e-8bf3-8ccc9bf97f2e (old id 8058530)
- date added to LUP
- 2016-04-01 09:49:53
- date last changed
- 2022-04-11 23:17:16
@article{95bed059-abfb-475e-8bf3-8ccc9bf97f2e,
abstract = {{The study of biomolecular interactions is central to an understanding of function, malfunction and therapeutic modulation of biological systems, yet often involves a compromise between sensitivity and accuracy. Many conventional analytical steps and the procedures required to facilitate sensitive detection, such as the incorporation of chemical labels, are prone to perturb the complexes under observation. Here we present a 'latent' analysis approach that uses chemical and microfluidic tools to reveal, through highly sensitive detection of a labelled system, the behaviour of the physiologically relevant unlabelled system. We implement this strategy in a native microfluidic diffusional sizing platform, allowing us to achieve detection sensitivity at the attomole level, determine the hydrodynamic radii of biomolecules that vary by over three orders of magnitude in molecular weight, and study heterogeneous mixtures. We illustrate these key advantages by characterizing a complex of an antibody domain in the solution phase and under physiologically relevant conditions.}},
author = {{Yates, Emma V. and Mueller, Thomas and Rajah, Luke and De Genst, Erwin J. and Arosio, Paolo and Linse, Sara and Vendruscolo, Michele and Dobson, Christopher M. and Knowles, Tuomas P. J.}},
issn = {{1755-4330}},
language = {{eng}},
number = {{10}},
pages = {{802--809}},
publisher = {{Nature Publishing Group}},
series = {{Nature Chemistry}},
title = {{Latent analysis of unmodified biomolecules and their complexes in solution with attomole detection sensitivity}},
url = {{http://dx.doi.org/10.1038/NCHEM.2344}},
doi = {{10.1038/NCHEM.2344}},
volume = {{7}},
year = {{2015}},
}