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Nanoscale, Voltage-Driven Application of Bioactive Substances onto Cells with Organized Topography.

Schobesberger, Sophie; Jönsson, Peter LU ; Buzuk, Andrey; Korchev, Yuri; Siggers, Jennifer and Gorelik, Julia (2016) In Biophysical Journal 110(1). p.141-146
Abstract
With scanning ion conductance microscopy (SICM), a noncontact scanning probe technique, it is possible both to obtain information about the surface topography of live cells and to apply molecules onto specific nanoscale structures. The technique is therefore widely used to apply chemical compounds and to study the properties of molecules on the surfaces of various cell types. The heart muscle cells, i.e., the cardiomyocytes, possess a highly elaborate, unique surface topography including transverse-tubule (T-tubule) openings leading into a cell internal system that exclusively harbors many proteins necessary for the cell's physiological function. Here, we applied isoproterenol into these surface openings by changing the applied voltage... (More)
With scanning ion conductance microscopy (SICM), a noncontact scanning probe technique, it is possible both to obtain information about the surface topography of live cells and to apply molecules onto specific nanoscale structures. The technique is therefore widely used to apply chemical compounds and to study the properties of molecules on the surfaces of various cell types. The heart muscle cells, i.e., the cardiomyocytes, possess a highly elaborate, unique surface topography including transverse-tubule (T-tubule) openings leading into a cell internal system that exclusively harbors many proteins necessary for the cell's physiological function. Here, we applied isoproterenol into these surface openings by changing the applied voltage over the SICM nanopipette. To determine the grade of precision of our application we used finite-element simulations to investigate how the concentration profile varies over the cell surface. We first obtained topography scans of the cardiomyocytes using SICM and then determined the electrophoretic mobility of isoproterenol in a high ion solution to be -7 × 10(-9) m(2)/V s. The simulations showed that the delivery to the T-tubule opening is highly confined to the underlying Z-groove, and especially to the first T-tubule opening, where the concentration is ∼6.5 times higher compared to on a flat surface under the same delivery settings. Delivery to the crest, instead of the T-tubule opening, resulted in a much lower concentration, emphasizing the importance of topography in agonist delivery. In conclusion, SICM, unlike other techniques, can reliably deliver precise quantities of compounds to the T-tubules of cardiomyocytes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biophysical Journal
volume
110
issue
1
pages
141 - 146
publisher
Cell Press
external identifiers
  • pmid:26745417
  • wos:000367783900006
  • scopus:84953261037
ISSN
1542-0086
DOI
10.1016/j.bpj.2015.11.017
language
English
LU publication?
yes
id
4cf5b49d-08f4-4b2c-a2fe-1cbaa9dd44e4 (old id 8592638)
date added to LUP
2016-02-10 14:01:57
date last changed
2017-01-01 04:03:11
@article{4cf5b49d-08f4-4b2c-a2fe-1cbaa9dd44e4,
  abstract     = {With scanning ion conductance microscopy (SICM), a noncontact scanning probe technique, it is possible both to obtain information about the surface topography of live cells and to apply molecules onto specific nanoscale structures. The technique is therefore widely used to apply chemical compounds and to study the properties of molecules on the surfaces of various cell types. The heart muscle cells, i.e., the cardiomyocytes, possess a highly elaborate, unique surface topography including transverse-tubule (T-tubule) openings leading into a cell internal system that exclusively harbors many proteins necessary for the cell's physiological function. Here, we applied isoproterenol into these surface openings by changing the applied voltage over the SICM nanopipette. To determine the grade of precision of our application we used finite-element simulations to investigate how the concentration profile varies over the cell surface. We first obtained topography scans of the cardiomyocytes using SICM and then determined the electrophoretic mobility of isoproterenol in a high ion solution to be -7 × 10(-9) m(2)/V s. The simulations showed that the delivery to the T-tubule opening is highly confined to the underlying Z-groove, and especially to the first T-tubule opening, where the concentration is ∼6.5 times higher compared to on a flat surface under the same delivery settings. Delivery to the crest, instead of the T-tubule opening, resulted in a much lower concentration, emphasizing the importance of topography in agonist delivery. In conclusion, SICM, unlike other techniques, can reliably deliver precise quantities of compounds to the T-tubules of cardiomyocytes.},
  author       = {Schobesberger, Sophie and Jönsson, Peter and Buzuk, Andrey and Korchev, Yuri and Siggers, Jennifer and Gorelik, Julia},
  issn         = {1542-0086},
  language     = {eng},
  number       = {1},
  pages        = {141--146},
  publisher    = {Cell Press},
  series       = {Biophysical Journal},
  title        = {Nanoscale, Voltage-Driven Application of Bioactive Substances onto Cells with Organized Topography.},
  url          = {http://dx.doi.org/10.1016/j.bpj.2015.11.017},
  volume       = {110},
  year         = {2016},
}