Cargando…

The uniformity and stability of cellular mass density in mammalian cell culture

Cell dry mass is principally determined by the sum of biosynthesis and degradation. Measurable change in dry mass occurs on a time scale of hours. By contrast, cell volume can change in minutes by altering the osmotic conditions. How changes in dry mass and volume are coupled is a fundamental questi...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Xili, Oh, Seungeun, Kirschner, Marc W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9597509/
https://www.ncbi.nlm.nih.gov/pubmed/36313562
http://dx.doi.org/10.3389/fcell.2022.1017499
_version_ 1784816107921604608
author Liu, Xili
Oh, Seungeun
Kirschner, Marc W.
author_facet Liu, Xili
Oh, Seungeun
Kirschner, Marc W.
author_sort Liu, Xili
collection PubMed
description Cell dry mass is principally determined by the sum of biosynthesis and degradation. Measurable change in dry mass occurs on a time scale of hours. By contrast, cell volume can change in minutes by altering the osmotic conditions. How changes in dry mass and volume are coupled is a fundamental question in cell size control. If cell volume were proportional to cell dry mass during growth, the cell would always maintain the same cellular mass density, defined as cell dry mass dividing by cell volume. The accuracy and stability against perturbation of this proportionality has never been stringently tested. Normalized Raman Imaging (NoRI), can measure both protein and lipid dry mass density directly. Using this new technique, we have been able to investigate the stability of mass density in response to pharmaceutical and physiological perturbations in three cultured mammalian cell lines. We find a remarkably narrow mass density distribution within cells, that is, significantly tighter than the variability of mass or volume distribution. The measured mass density is independent of the cell cycle. We find that mass density can be modulated directly by extracellular osmolytes or by disruptions of the cytoskeleton. Yet, mass density is surprisingly resistant to pharmacological perturbations of protein synthesis or protein degradation, suggesting there must be some form of feedback control to maintain the homeostasis of mass density when mass is altered. By contrast, physiological perturbations such as starvation or senescence induce significant shifts in mass density. We have begun to shed light on how and why cell mass density remains fixed against some perturbations and yet is sensitive during transitions in physiological state.
format Online
Article
Text
id pubmed-9597509
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95975092022-10-27 The uniformity and stability of cellular mass density in mammalian cell culture Liu, Xili Oh, Seungeun Kirschner, Marc W. Front Cell Dev Biol Cell and Developmental Biology Cell dry mass is principally determined by the sum of biosynthesis and degradation. Measurable change in dry mass occurs on a time scale of hours. By contrast, cell volume can change in minutes by altering the osmotic conditions. How changes in dry mass and volume are coupled is a fundamental question in cell size control. If cell volume were proportional to cell dry mass during growth, the cell would always maintain the same cellular mass density, defined as cell dry mass dividing by cell volume. The accuracy and stability against perturbation of this proportionality has never been stringently tested. Normalized Raman Imaging (NoRI), can measure both protein and lipid dry mass density directly. Using this new technique, we have been able to investigate the stability of mass density in response to pharmaceutical and physiological perturbations in three cultured mammalian cell lines. We find a remarkably narrow mass density distribution within cells, that is, significantly tighter than the variability of mass or volume distribution. The measured mass density is independent of the cell cycle. We find that mass density can be modulated directly by extracellular osmolytes or by disruptions of the cytoskeleton. Yet, mass density is surprisingly resistant to pharmacological perturbations of protein synthesis or protein degradation, suggesting there must be some form of feedback control to maintain the homeostasis of mass density when mass is altered. By contrast, physiological perturbations such as starvation or senescence induce significant shifts in mass density. We have begun to shed light on how and why cell mass density remains fixed against some perturbations and yet is sensitive during transitions in physiological state. Frontiers Media S.A. 2022-10-12 /pmc/articles/PMC9597509/ /pubmed/36313562 http://dx.doi.org/10.3389/fcell.2022.1017499 Text en Copyright © 2022 Liu, Oh and Kirschner. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Liu, Xili
Oh, Seungeun
Kirschner, Marc W.
The uniformity and stability of cellular mass density in mammalian cell culture
title The uniformity and stability of cellular mass density in mammalian cell culture
title_full The uniformity and stability of cellular mass density in mammalian cell culture
title_fullStr The uniformity and stability of cellular mass density in mammalian cell culture
title_full_unstemmed The uniformity and stability of cellular mass density in mammalian cell culture
title_short The uniformity and stability of cellular mass density in mammalian cell culture
title_sort uniformity and stability of cellular mass density in mammalian cell culture
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9597509/
https://www.ncbi.nlm.nih.gov/pubmed/36313562
http://dx.doi.org/10.3389/fcell.2022.1017499
work_keys_str_mv AT liuxili theuniformityandstabilityofcellularmassdensityinmammaliancellculture
AT ohseungeun theuniformityandstabilityofcellularmassdensityinmammaliancellculture
AT kirschnermarcw theuniformityandstabilityofcellularmassdensityinmammaliancellculture
AT liuxili uniformityandstabilityofcellularmassdensityinmammaliancellculture
AT ohseungeun uniformityandstabilityofcellularmassdensityinmammaliancellculture
AT kirschnermarcw uniformityandstabilityofcellularmassdensityinmammaliancellculture