Modeling the Transport of Nuclear Proteins Along Single Skeletal Muscle Cells
type: Dataset
description: The purpose of this study was to define the factors that control the distribution of nuclear proteins in multinucleated skeletal muscle cells (myotubes). Nuclear-targeted red fluorescent proteins of different molecular weights were used as a model protein. Changes in their distributions were quantified as a result of perturbations causing myotube hypertrophy, atrophy, and diminished nuclear import rates. A computational model was developed to simulate nuclear protein distribution using a combination of empirical values and data from the literature. Finally, the results from the model system were then validated using muscle-related transcription factors ARNT and Six1. These data were generated to study the distribution of nuclear proteins within multi-nucleated skeletal muscle cells. Myotubes were produced by differentiating primary mouse myoblasts that were sparsely transfected to express a nuclear protein from a single nucleus. From the microscopy images, we measured the protein intensity in all nuclei along with the distance of each nucleus from the brightest one, which was assumed to be the transfected nucleus. We used these distribution profiles to study the relationship between protein size and its transport behavior. We also studied the effect of treatments that induce cell hypertrophy (capsaicin), atrophy (dexamethasone), and diminished nuclear import (importazole) on the transport of the nuclear proteins. We also developed a mathematical model to simulate how changes in cell and protein properties affect protein transport. These data form the basis of the figures in the associated manuscript, and the detailed methods pertaining to their collection can be found there. The data have been organized according to their corresponding figure. Figure 1 - Nuclear protein transport dynamics Using time-lapse microscopy, we captured the transport of the DsRed red fluorescent protein (RFP) at 6, 12, 18, and 24 hours after induction of expression (Fig 1 - 1-4). We also in…
citation: CreativeWork
  name: Modeling the transport of nuclear proteins along single skeletal muscle cells. Hermes Taylor-Weiner, Christopher L. Grigsby, Duarte M. S. Ferreira, José M. Dias, Molly M. Stevens, Jorge L. Ruas, Ana I. Teixeira. Proceedings of the National Academy of Sciences, Jan 2020, 201919600; DOI: 10.1073/pnas.1919600117
conditions of access: https://publications.europa.eu/resource/authority/access-right/NON_PUBLIC
conditions of access: info:eu-repo/semantics/restrictedAccess
contributor: Christopher Grigsby
creative work status: completed
  type: DefinedTerm
  in defined term set: http://publications.europa.eu/resource/authority/dataset-status
  term code: COMPLETED
creator: Ana Teixeira
date modified: 2026-04-08
date published: 2020-02-19
funding: Spatial signalling in cell-to-cell communication
  type: Grant
  description: Cell-to-cell communication pathways coordinate cellular functions in multicellular organisms and are frequently dysregulated in cancer, allowing cells to acquire abnormal functions such as invasion of neighboring tissues. Membrane proteins are key sensor components in cell-to-cell communication and form the largest class of proteins in the druggable genome. We hypothesize that the spatial distribution of ligands and receptors contributes to defining the fundamental mechanisms of action of cell-to-cell communication pathways and their cellular outcomes. The research program relies on the development of tools that provide well-defined physical inputs to cells, not confounded by simultaneous changes in chemical inputs. Therefore, beyond state-of-the-art developments in nanotechnology are here integrated with cell biology. In particular, DNA origami technology is applied to the development of ligand nanoclusters with customized spatial organization and mechanical properties. We will focus on the ephrin/Eph and DSL/Notch cell-to-cell communication pathways, which regulate embryonic development and the homeostasis of adult organs. These pathways are commonly disrupted in cancer, showing tumour suppressing or tumour promoting character. The mechanisms that generate the diversity of outcomes in normal and disease settings are largely unknown. We will use DNA origami/ephrin ligand nanoclusters to investigate whether the spatial organization ligand assemblies impact receptor function. We aim to generate a knowledge foundation for the development of new rational therapeutic approaches that target ephrin ligand/Eph and Notch receptor signalling.
  funder: Swedish Research Council
language: English
is part of: https://doi.org/10.5878/8m35-h707
keywords: Medical Modelling and Simulation
  type: DefinedTerm
  term code: 20605
keywords: Medical and Health Sciences
  type: DefinedTerm
  term code: 3
keywords: Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
  type: DefinedTerm
  term code: 30401
keywords: Nanotechnology for/in Life Science and Medicine
  type: DefinedTerm
  term code: 21005
keywords: skeletal muscle
keywords: mathematical model
keywords: myonuclear domain
keywords: nuclear transport
publisher: Karolinska Institutet
version: 1.0

PropertyValue
property ID: DOI
value: 10.5878/2hjy-e586

principalRegistrationNumber
type: PropertyValue
property ID: https://www.rikstermbanken.se/termposter/1848/diarienummer
value: 1

PropertyValue
property ID: DOI
value: 10.1073/pnas.1919600117

Christopher Grigsby
type: Person
affiliation: Karolinska Institutet
family name: Grigsby
given name: Christopher

Karolinska Institutet
type: Organization
department: Department of Medical Biochemistry and Biophysics

Ana Teixeira
type: Person
affiliation: Karolinska Institutet
family name: Teixeira
given name: Ana

Swedish Research Council
type: Organization

English
type: Language
alternate name: eng