Integrin-mediated mechanotransduction in vascular smooth muscle cells: Frequency and force response characteristics

M. E. Goldschmidt, K. J. McLeod, W. R. Taylor

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Blood vessels are continuously exposed to mechanical forces that lead to adaptive remodeling and atherosclerosis. Although there have been many studies characterizing the responses of vascular cells to mechanical stimuli, the precise mechanical characteristics of the forces applied to cells to elicit these responses are not clear. We designed a magnetic exposure system capable of producing a defined normal force on ferromagnetic beads that are specifically bound to cultured cells coated with extracellular matrix proteins or integrin-specific antibodies. Rat aortic smooth muscle cells were incubated with engineered fibronectin - coated ferromagnetic beads and then exposed to a magnetic field. With activation of extracellular signal - regulated mitogen-activated protein kinase 1/2 (ERK 1/2MAPK) used as a prototypical marker for cell responsiveness to mechanical forces, Western blot analysis demonstrated an increase in phosphorylated ERK 1/2MAPK expression reaching a maximal response of a 3.5-fold increase at a total force of ≈2.5 pN per cell. The peak response occurred after 5 minutes of exposure and slowly decreased to baseline after 30 minutes. A cyclic, rather than static, force was required for this activation, and the frequency-response curve increased ≈2-fold between 0.5 and 2.0 Hz. Vitronectin- and β3 antibody-coated beads showed a response nearly identical to those coated with engineered fibronectin, whereas forces applied to beads coated with α2 and β1 antibodies did not significantly activate ERK 1/2MAPK. Mechanical activation of the ERK 1/2MAPK system in rat aortic smooth muscle cells occurs through specific integrin receptors and requires a cyclic force with a magnitude estimated to be in the piconewton range.

Original languageEnglish (US)
Pages (from-to)674-680
Number of pages7
JournalCirculation Research
Volume88
Issue number7
DOIs
StatePublished - Apr 13 2001

Fingerprint

Vascular Smooth Muscle
Integrins
Smooth Muscle Myocytes
Mitogen-Activated Protein Kinase 1
Fibronectins
Blood Vessels
Antibodies
Vitronectin
Extracellular Matrix Proteins
Magnetic Fields
Cultured Cells
Atherosclerosis
Western Blotting

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{c870d0599aed41ed95f5bd55f948bcd7,
title = "Integrin-mediated mechanotransduction in vascular smooth muscle cells: Frequency and force response characteristics",
abstract = "Blood vessels are continuously exposed to mechanical forces that lead to adaptive remodeling and atherosclerosis. Although there have been many studies characterizing the responses of vascular cells to mechanical stimuli, the precise mechanical characteristics of the forces applied to cells to elicit these responses are not clear. We designed a magnetic exposure system capable of producing a defined normal force on ferromagnetic beads that are specifically bound to cultured cells coated with extracellular matrix proteins or integrin-specific antibodies. Rat aortic smooth muscle cells were incubated with engineered fibronectin - coated ferromagnetic beads and then exposed to a magnetic field. With activation of extracellular signal - regulated mitogen-activated protein kinase 1/2 (ERK 1/2MAPK) used as a prototypical marker for cell responsiveness to mechanical forces, Western blot analysis demonstrated an increase in phosphorylated ERK 1/2MAPK expression reaching a maximal response of a 3.5-fold increase at a total force of ≈2.5 pN per cell. The peak response occurred after 5 minutes of exposure and slowly decreased to baseline after 30 minutes. A cyclic, rather than static, force was required for this activation, and the frequency-response curve increased ≈2-fold between 0.5 and 2.0 Hz. Vitronectin- and β3 antibody-coated beads showed a response nearly identical to those coated with engineered fibronectin, whereas forces applied to beads coated with α2 and β1 antibodies did not significantly activate ERK 1/2MAPK. Mechanical activation of the ERK 1/2MAPK system in rat aortic smooth muscle cells occurs through specific integrin receptors and requires a cyclic force with a magnitude estimated to be in the piconewton range.",
author = "Goldschmidt, {M. E.} and McLeod, {K. J.} and Taylor, {W. R.}",
year = "2001",
month = "4",
day = "13",
doi = "10.1161/hh0701.089749",
language = "English (US)",
volume = "88",
pages = "674--680",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

Integrin-mediated mechanotransduction in vascular smooth muscle cells : Frequency and force response characteristics. / Goldschmidt, M. E.; McLeod, K. J.; Taylor, W. R.

In: Circulation Research, Vol. 88, No. 7, 13.04.2001, p. 674-680.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Integrin-mediated mechanotransduction in vascular smooth muscle cells

T2 - Frequency and force response characteristics

AU - Goldschmidt, M. E.

AU - McLeod, K. J.

AU - Taylor, W. R.

PY - 2001/4/13

Y1 - 2001/4/13

N2 - Blood vessels are continuously exposed to mechanical forces that lead to adaptive remodeling and atherosclerosis. Although there have been many studies characterizing the responses of vascular cells to mechanical stimuli, the precise mechanical characteristics of the forces applied to cells to elicit these responses are not clear. We designed a magnetic exposure system capable of producing a defined normal force on ferromagnetic beads that are specifically bound to cultured cells coated with extracellular matrix proteins or integrin-specific antibodies. Rat aortic smooth muscle cells were incubated with engineered fibronectin - coated ferromagnetic beads and then exposed to a magnetic field. With activation of extracellular signal - regulated mitogen-activated protein kinase 1/2 (ERK 1/2MAPK) used as a prototypical marker for cell responsiveness to mechanical forces, Western blot analysis demonstrated an increase in phosphorylated ERK 1/2MAPK expression reaching a maximal response of a 3.5-fold increase at a total force of ≈2.5 pN per cell. The peak response occurred after 5 minutes of exposure and slowly decreased to baseline after 30 minutes. A cyclic, rather than static, force was required for this activation, and the frequency-response curve increased ≈2-fold between 0.5 and 2.0 Hz. Vitronectin- and β3 antibody-coated beads showed a response nearly identical to those coated with engineered fibronectin, whereas forces applied to beads coated with α2 and β1 antibodies did not significantly activate ERK 1/2MAPK. Mechanical activation of the ERK 1/2MAPK system in rat aortic smooth muscle cells occurs through specific integrin receptors and requires a cyclic force with a magnitude estimated to be in the piconewton range.

AB - Blood vessels are continuously exposed to mechanical forces that lead to adaptive remodeling and atherosclerosis. Although there have been many studies characterizing the responses of vascular cells to mechanical stimuli, the precise mechanical characteristics of the forces applied to cells to elicit these responses are not clear. We designed a magnetic exposure system capable of producing a defined normal force on ferromagnetic beads that are specifically bound to cultured cells coated with extracellular matrix proteins or integrin-specific antibodies. Rat aortic smooth muscle cells were incubated with engineered fibronectin - coated ferromagnetic beads and then exposed to a magnetic field. With activation of extracellular signal - regulated mitogen-activated protein kinase 1/2 (ERK 1/2MAPK) used as a prototypical marker for cell responsiveness to mechanical forces, Western blot analysis demonstrated an increase in phosphorylated ERK 1/2MAPK expression reaching a maximal response of a 3.5-fold increase at a total force of ≈2.5 pN per cell. The peak response occurred after 5 minutes of exposure and slowly decreased to baseline after 30 minutes. A cyclic, rather than static, force was required for this activation, and the frequency-response curve increased ≈2-fold between 0.5 and 2.0 Hz. Vitronectin- and β3 antibody-coated beads showed a response nearly identical to those coated with engineered fibronectin, whereas forces applied to beads coated with α2 and β1 antibodies did not significantly activate ERK 1/2MAPK. Mechanical activation of the ERK 1/2MAPK system in rat aortic smooth muscle cells occurs through specific integrin receptors and requires a cyclic force with a magnitude estimated to be in the piconewton range.

UR - http://www.scopus.com/inward/record.url?scp=0035853388&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035853388&partnerID=8YFLogxK

U2 - 10.1161/hh0701.089749

DO - 10.1161/hh0701.089749

M3 - Article

C2 - 11304489

AN - SCOPUS:0035853388

VL - 88

SP - 674

EP - 680

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 7

ER -