Alignment of corneal and lens epithelial cells by co-operative effects of substratum topography and DC electric fields

Ann M. Rajnicek, Louise E. Foubister, Colin D. McCaig

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Corneal and lens epithelial cells (CECs and LECs) in the eye encounter precisely ordered fibre arrays on the nanoscale in tandem with an endogenous electric field (EF). Prosthetic biomaterials often incorporate topographical features intended to mimic those in situ. However, the cellular basis for control of cell morphology by nanotopography or by an EF is not clear. We examined cell axis alignment in response to substratum nanotopography and a physiological EF separately and in combination. Bovine CECs aligned parallel to substratum nanogrooves (NGs) as shallow as 14 nm but LECs were less sensitive. Actin filaments of both cell types concentrated at substratum ridges so we tested the mechanistic roles of rho, rac and cdc42, molecules that control cytoskeletal organization. CEC alignment to 130 nm deep NGs was prevented by the inhibition of rho, but not by the inhibition of cdc42, rac, or the rho effectors myosin light chain kinase or rho kinase. Conversely, CEC alignment was enhanced by the activation of rho. CECs on planar quartz substrata aligned orthogonal to an EF of 150 mV/mm. Alignment required signalling by cdc42 and rho but not rac, and was accompanied by lamellipodial reorganisation and cell migration toward the cathode. When CECs on vertically oriented NGs were exposed simultaneously to a horizontal EF, they aligned more robustly than to either cue alone and the enhanced alignment required rho signalling. Therefore, nanoscale substratum features and EFs co-operate to control cell axis alignment via rho, and cdc42-mediated intracellular signals, which can be exploited in tissue engineering. (c) 2008 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)2082-2095
Number of pages14
JournalBiomaterials
Volume29
Issue number13
DOIs
Publication statusPublished - May 2008

Keywords

  • cornea
  • lens
  • wound healing
  • nanotopography
  • cytoskeleton
  • rho GTPases
  • microgrooved surfaces
  • mechanical-properties
  • contact guidance
  • scale topography
  • collagen fibril
  • in-vivo
  • orientation
  • migration
  • fibroblasts
  • RHO

Cite this

Alignment of corneal and lens epithelial cells by co-operative effects of substratum topography and DC electric fields. / Rajnicek, Ann M.; Foubister, Louise E.; McCaig, Colin D.

In: Biomaterials, Vol. 29, No. 13, 05.2008, p. 2082-2095.

Research output: Contribution to journalArticle

@article{85f73aef8ae9479fab90190d1b829657,
title = "Alignment of corneal and lens epithelial cells by co-operative effects of substratum topography and DC electric fields",
abstract = "Corneal and lens epithelial cells (CECs and LECs) in the eye encounter precisely ordered fibre arrays on the nanoscale in tandem with an endogenous electric field (EF). Prosthetic biomaterials often incorporate topographical features intended to mimic those in situ. However, the cellular basis for control of cell morphology by nanotopography or by an EF is not clear. We examined cell axis alignment in response to substratum nanotopography and a physiological EF separately and in combination. Bovine CECs aligned parallel to substratum nanogrooves (NGs) as shallow as 14 nm but LECs were less sensitive. Actin filaments of both cell types concentrated at substratum ridges so we tested the mechanistic roles of rho, rac and cdc42, molecules that control cytoskeletal organization. CEC alignment to 130 nm deep NGs was prevented by the inhibition of rho, but not by the inhibition of cdc42, rac, or the rho effectors myosin light chain kinase or rho kinase. Conversely, CEC alignment was enhanced by the activation of rho. CECs on planar quartz substrata aligned orthogonal to an EF of 150 mV/mm. Alignment required signalling by cdc42 and rho but not rac, and was accompanied by lamellipodial reorganisation and cell migration toward the cathode. When CECs on vertically oriented NGs were exposed simultaneously to a horizontal EF, they aligned more robustly than to either cue alone and the enhanced alignment required rho signalling. Therefore, nanoscale substratum features and EFs co-operate to control cell axis alignment via rho, and cdc42-mediated intracellular signals, which can be exploited in tissue engineering. (c) 2008 Elsevier Ltd. All rights reserved.",
keywords = "cornea, lens, wound healing, nanotopography, cytoskeleton, rho GTPases, microgrooved surfaces, mechanical-properties, contact guidance, scale topography, collagen fibril , in-vivo, orientation, migration, fibroblasts, RHO",
author = "Rajnicek, {Ann M.} and Foubister, {Louise E.} and McCaig, {Colin D.}",
year = "2008",
month = "5",
doi = "10.1016/j.biomaterials.2008.01.015",
language = "English",
volume = "29",
pages = "2082--2095",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
number = "13",

}

TY - JOUR

T1 - Alignment of corneal and lens epithelial cells by co-operative effects of substratum topography and DC electric fields

AU - Rajnicek, Ann M.

AU - Foubister, Louise E.

AU - McCaig, Colin D.

PY - 2008/5

Y1 - 2008/5

N2 - Corneal and lens epithelial cells (CECs and LECs) in the eye encounter precisely ordered fibre arrays on the nanoscale in tandem with an endogenous electric field (EF). Prosthetic biomaterials often incorporate topographical features intended to mimic those in situ. However, the cellular basis for control of cell morphology by nanotopography or by an EF is not clear. We examined cell axis alignment in response to substratum nanotopography and a physiological EF separately and in combination. Bovine CECs aligned parallel to substratum nanogrooves (NGs) as shallow as 14 nm but LECs were less sensitive. Actin filaments of both cell types concentrated at substratum ridges so we tested the mechanistic roles of rho, rac and cdc42, molecules that control cytoskeletal organization. CEC alignment to 130 nm deep NGs was prevented by the inhibition of rho, but not by the inhibition of cdc42, rac, or the rho effectors myosin light chain kinase or rho kinase. Conversely, CEC alignment was enhanced by the activation of rho. CECs on planar quartz substrata aligned orthogonal to an EF of 150 mV/mm. Alignment required signalling by cdc42 and rho but not rac, and was accompanied by lamellipodial reorganisation and cell migration toward the cathode. When CECs on vertically oriented NGs were exposed simultaneously to a horizontal EF, they aligned more robustly than to either cue alone and the enhanced alignment required rho signalling. Therefore, nanoscale substratum features and EFs co-operate to control cell axis alignment via rho, and cdc42-mediated intracellular signals, which can be exploited in tissue engineering. (c) 2008 Elsevier Ltd. All rights reserved.

AB - Corneal and lens epithelial cells (CECs and LECs) in the eye encounter precisely ordered fibre arrays on the nanoscale in tandem with an endogenous electric field (EF). Prosthetic biomaterials often incorporate topographical features intended to mimic those in situ. However, the cellular basis for control of cell morphology by nanotopography or by an EF is not clear. We examined cell axis alignment in response to substratum nanotopography and a physiological EF separately and in combination. Bovine CECs aligned parallel to substratum nanogrooves (NGs) as shallow as 14 nm but LECs were less sensitive. Actin filaments of both cell types concentrated at substratum ridges so we tested the mechanistic roles of rho, rac and cdc42, molecules that control cytoskeletal organization. CEC alignment to 130 nm deep NGs was prevented by the inhibition of rho, but not by the inhibition of cdc42, rac, or the rho effectors myosin light chain kinase or rho kinase. Conversely, CEC alignment was enhanced by the activation of rho. CECs on planar quartz substrata aligned orthogonal to an EF of 150 mV/mm. Alignment required signalling by cdc42 and rho but not rac, and was accompanied by lamellipodial reorganisation and cell migration toward the cathode. When CECs on vertically oriented NGs were exposed simultaneously to a horizontal EF, they aligned more robustly than to either cue alone and the enhanced alignment required rho signalling. Therefore, nanoscale substratum features and EFs co-operate to control cell axis alignment via rho, and cdc42-mediated intracellular signals, which can be exploited in tissue engineering. (c) 2008 Elsevier Ltd. All rights reserved.

KW - cornea

KW - lens

KW - wound healing

KW - nanotopography

KW - cytoskeleton

KW - rho GTPases

KW - microgrooved surfaces

KW - mechanical-properties

KW - contact guidance

KW - scale topography

KW - collagen fibril

KW - in-vivo

KW - orientation

KW - migration

KW - fibroblasts

KW - RHO

U2 - 10.1016/j.biomaterials.2008.01.015

DO - 10.1016/j.biomaterials.2008.01.015

M3 - Article

VL - 29

SP - 2082

EP - 2095

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 13

ER -