The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates

Jamal S. Lewis, Natalia V. Dolgova, Thomas J. Chancellor, Abhinav P. Acharya, Jerome V. Karpiak, Tanmay P. Lele, Benjamin G. Keselowsky

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine invivo, it is reasonable to postulate DCs experience the mechanical forces in such mechanically active tissues. However, it is currently unknown how DCs respond to cyclic mechanical strain. In order to explore the hypothesis that DCs are responsive to mechanical strain, DCs were cultured invitro on pre-adsorbed adhesive proteins (e.g., laminin, collagen, fibrinogen) and 1Hz cyclic strain was applied for various durations and strain magnitudes. It was determined that a strain magnitude of 10% and 24h duration adversely affected DC viability compared to no-strain controls, but culture on certain adhesive substrates provided modest protection of viability under this harsh strain regime. In contrast, application of 1h of 1Hz cyclic 3% strain did not affect DC viability and this strain regime was used for the remaining experiments for quantifying DC activation and T-cell priming capability. Application of 3% strain increased expression of stimulatory (MHC-II) and costimulatory molecules (CD86, CD40), and this effect was generally increased by culture on pre-coated adhesive substrates. Interestingly, the cytokine secretion profile of DCs was not significantly affected by strain. Lastly, strained DCs demonstrated increased stimulation of allogeneic T-cell proliferation, in a manner that was independent of the adhesive substrate. These observations indicate generation of a DC consistent with what has been described as a semi-mature phenotype. This work begins elucidating a potential role for DCs in tissue environments exposed to cyclic mechanical forces.

Original languageEnglish (US)
Pages (from-to)9063-9070
Number of pages8
JournalBiomaterials
Volume34
Issue number36
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

Fingerprint

Adhesives
Dendritic Cells
Chemical activation
Substrates
T-cells
Tissue
Cell Survival
Strain control
T-Lymphocytes
Pulsatile Flow
Cell proliferation
Laminin
Collagen
Fibrinogen
Immunity
Blood
Cell Proliferation
Cytokines
Proteins
Phenotype

Keywords

  • Cell adhesion
  • Dendritic cells
  • Extracellular matrix
  • Immunology
  • Mechanical force
  • Mechanical strain

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Lewis, J. S., Dolgova, N. V., Chancellor, T. J., Acharya, A. P., Karpiak, J. V., Lele, T. P., & Keselowsky, B. G. (2013). The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates. Biomaterials, 34(36), 9063-9070. https://doi.org/10.1016/j.biomaterials.2013.08.021

The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates. / Lewis, Jamal S.; Dolgova, Natalia V.; Chancellor, Thomas J.; Acharya, Abhinav P.; Karpiak, Jerome V.; Lele, Tanmay P.; Keselowsky, Benjamin G.

In: Biomaterials, Vol. 34, No. 36, 01.12.2013, p. 9063-9070.

Research output: Contribution to journalArticle

Lewis, JS, Dolgova, NV, Chancellor, TJ, Acharya, AP, Karpiak, JV, Lele, TP & Keselowsky, BG 2013, 'The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates', Biomaterials, vol. 34, no. 36, pp. 9063-9070. https://doi.org/10.1016/j.biomaterials.2013.08.021
Lewis, Jamal S. ; Dolgova, Natalia V. ; Chancellor, Thomas J. ; Acharya, Abhinav P. ; Karpiak, Jerome V. ; Lele, Tanmay P. ; Keselowsky, Benjamin G. / The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates. In: Biomaterials. 2013 ; Vol. 34, No. 36. pp. 9063-9070.
@article{4661243c6cd24e4b92b691af0b25619b,
title = "The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates",
abstract = "Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine invivo, it is reasonable to postulate DCs experience the mechanical forces in such mechanically active tissues. However, it is currently unknown how DCs respond to cyclic mechanical strain. In order to explore the hypothesis that DCs are responsive to mechanical strain, DCs were cultured invitro on pre-adsorbed adhesive proteins (e.g., laminin, collagen, fibrinogen) and 1Hz cyclic strain was applied for various durations and strain magnitudes. It was determined that a strain magnitude of 10{\%} and 24h duration adversely affected DC viability compared to no-strain controls, but culture on certain adhesive substrates provided modest protection of viability under this harsh strain regime. In contrast, application of 1h of 1Hz cyclic 3{\%} strain did not affect DC viability and this strain regime was used for the remaining experiments for quantifying DC activation and T-cell priming capability. Application of 3{\%} strain increased expression of stimulatory (MHC-II) and costimulatory molecules (CD86, CD40), and this effect was generally increased by culture on pre-coated adhesive substrates. Interestingly, the cytokine secretion profile of DCs was not significantly affected by strain. Lastly, strained DCs demonstrated increased stimulation of allogeneic T-cell proliferation, in a manner that was independent of the adhesive substrate. These observations indicate generation of a DC consistent with what has been described as a semi-mature phenotype. This work begins elucidating a potential role for DCs in tissue environments exposed to cyclic mechanical forces.",
keywords = "Cell adhesion, Dendritic cells, Extracellular matrix, Immunology, Mechanical force, Mechanical strain",
author = "Lewis, {Jamal S.} and Dolgova, {Natalia V.} and Chancellor, {Thomas J.} and Acharya, {Abhinav P.} and Karpiak, {Jerome V.} and Lele, {Tanmay P.} and Keselowsky, {Benjamin G.}",
year = "2013",
month = "12",
day = "1",
doi = "10.1016/j.biomaterials.2013.08.021",
language = "English (US)",
volume = "34",
pages = "9063--9070",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "36",

}

TY - JOUR

T1 - The effect of cyclic mechanical strain on activation of dendritic cells cultured on adhesive substrates

AU - Lewis, Jamal S.

AU - Dolgova, Natalia V.

AU - Chancellor, Thomas J.

AU - Acharya, Abhinav P.

AU - Karpiak, Jerome V.

AU - Lele, Tanmay P.

AU - Keselowsky, Benjamin G.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine invivo, it is reasonable to postulate DCs experience the mechanical forces in such mechanically active tissues. However, it is currently unknown how DCs respond to cyclic mechanical strain. In order to explore the hypothesis that DCs are responsive to mechanical strain, DCs were cultured invitro on pre-adsorbed adhesive proteins (e.g., laminin, collagen, fibrinogen) and 1Hz cyclic strain was applied for various durations and strain magnitudes. It was determined that a strain magnitude of 10% and 24h duration adversely affected DC viability compared to no-strain controls, but culture on certain adhesive substrates provided modest protection of viability under this harsh strain regime. In contrast, application of 1h of 1Hz cyclic 3% strain did not affect DC viability and this strain regime was used for the remaining experiments for quantifying DC activation and T-cell priming capability. Application of 3% strain increased expression of stimulatory (MHC-II) and costimulatory molecules (CD86, CD40), and this effect was generally increased by culture on pre-coated adhesive substrates. Interestingly, the cytokine secretion profile of DCs was not significantly affected by strain. Lastly, strained DCs demonstrated increased stimulation of allogeneic T-cell proliferation, in a manner that was independent of the adhesive substrate. These observations indicate generation of a DC consistent with what has been described as a semi-mature phenotype. This work begins elucidating a potential role for DCs in tissue environments exposed to cyclic mechanical forces.

AB - Dendritic cells (DCs), key regulators of tolerance and immunity, have been found to reside in mechanically active tissues such as the interior layers of the arterial wall, which experience cyclic radial wall strain due to pulsatile blood flow. Although experimentally difficult to determine invivo, it is reasonable to postulate DCs experience the mechanical forces in such mechanically active tissues. However, it is currently unknown how DCs respond to cyclic mechanical strain. In order to explore the hypothesis that DCs are responsive to mechanical strain, DCs were cultured invitro on pre-adsorbed adhesive proteins (e.g., laminin, collagen, fibrinogen) and 1Hz cyclic strain was applied for various durations and strain magnitudes. It was determined that a strain magnitude of 10% and 24h duration adversely affected DC viability compared to no-strain controls, but culture on certain adhesive substrates provided modest protection of viability under this harsh strain regime. In contrast, application of 1h of 1Hz cyclic 3% strain did not affect DC viability and this strain regime was used for the remaining experiments for quantifying DC activation and T-cell priming capability. Application of 3% strain increased expression of stimulatory (MHC-II) and costimulatory molecules (CD86, CD40), and this effect was generally increased by culture on pre-coated adhesive substrates. Interestingly, the cytokine secretion profile of DCs was not significantly affected by strain. Lastly, strained DCs demonstrated increased stimulation of allogeneic T-cell proliferation, in a manner that was independent of the adhesive substrate. These observations indicate generation of a DC consistent with what has been described as a semi-mature phenotype. This work begins elucidating a potential role for DCs in tissue environments exposed to cyclic mechanical forces.

KW - Cell adhesion

KW - Dendritic cells

KW - Extracellular matrix

KW - Immunology

KW - Mechanical force

KW - Mechanical strain

UR - http://www.scopus.com/inward/record.url?scp=84883754605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883754605&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2013.08.021

DO - 10.1016/j.biomaterials.2013.08.021

M3 - Article

C2 - 24008042

AN - SCOPUS:84883754605

VL - 34

SP - 9063

EP - 9070

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 36

ER -