Biomedical Engineering Reference
In-Depth Information
S4700 5.0 kV
27.9 mm ×2.00k SE(L)
11/2/06
20.0 µm
706IC-0489
2.5 kV
SE(U,-2.5)
1.00 µm
706IC-0463
5.0 kV SE(L,-40)
50.0 µm
(a)
(b)
(c)
Figure 20.4
Nanoscale.topographical.features.inluence.cellular.spreading.and.focal.adhesion.formation..(a).Nanoprotrusion.
with.microscale.x-y.dimensions.and.a.z-dimension.less.than.73.nm.increases.cellular.spreading..Nanoisland.
topography.increases.cellular.spreading.by.providing.tactile.stimuli..(b).Immuno-gold.labeling.of.focal.adhe-
sions. in. adherent. cells. (electron. dense. clusters). allows. the. visualization. of. cell-substratum. interactions. in.
adherent. cells.. Nanoscale. pits. >73.nm. in. diameter. perturb. integrin. clustering. (black. arrows),. forcing. adhe-
sion. formation. to. occur. at. the. interpit. regions.. (c). Focal. adhesions. as. visualized. by. SEM. and. immuno-gold.
labeling. indicate. that. grooves. with. z-dimensions. down. to. a. minimum. 30-40.nm. can. induce. adhesion. align-
ment.to.the.groove.orientation..(Reprinted.from. Nanomedicine ,.6(5),.Biggs,.M.J.,.Richards,.R.G.,.and.Dalby,.M.J.,.
Nanotopographical.modiication:.A.regulator.of.cellular.function.through.focal.adhesions,.619-633,.Copyright.
2010,.with.permission.from.Elsevier.)
composition,.orientation,.or.conformation.of.the.adsorbed.ECM.components;.Andersson.
et.al..2003b;.Martines.et.al..2005)..Of.particular.interest.is.the.temporospatial.reorganization.
of.the.cell.cytoskeleton.and.of.focal.adhesion.formation.in.response.to.nanofeatures.(Clark.
et. al.. 1987;. Dalby. et. al.. 2008a),. parameters. that. have. already. been. established. as. impor-
tant.mediators.of.mechanotransductive.processes.(Mack.et.al..2004).and.differential.gene.
expression.(Biggs.et.al..2009a,b)..Initiation.of.the.adhesive.process,.however,.is.dependent.
on.integrin.interactions.with.ECM.proteins.adsorbed.to.the.substratum.and.the.formation.
of.focal.adhesions,.processes.that.seem.to.be.dependent.on.the.symmetry.and.spacing.as.
well.as.the.x,.y,.and.z.dimensions.of.the.topographical.nanofeatures.(Figure.20.4).(Curtis.
et.al..2001;.Sato.et.al..2008)..Studies.with.deined.arrays.of.bound.RGD.fragments.indicate.
that. integrin-substratum. interactions. are. disrupted. when. the. integrin. spacing. is. in. the.
range.of.70-300.nm.and.that.an.integrin.spacing.of.less.than.approximately.58-73.nm.is.
required.for.protein.recruitment.to.the.focal.adhesion.(Arnold.et.al..2004;.Selhuber-Unkel.
et.al..2008)..Hence,.it.can.be.inferred.that.decreasing.the.nanofeature.spacing.to.less.than.
58-73.nm.or.increasing.this.distance.to.the.submicron.range.facilitates.integrin.clustering,.
thus.restoring.focal.adhesion.formation.
20.5 Effects of Nanoscale Protrusions on Focal Adhesion Formation
Nanoprotrusions.and.raised.topographical.features.have.been.reported.within.the.ECM.
in. a. large. number. of. tissues. (Tsuprun. and. Santi. 1999;. Bosman. and. Stamenkovic. 2003;.
Osawa.et.al..2003;.Bozec.and.Horton.2006)..Studies.of.cell.adhesion.on.nanoscale.protru-
sions.have.increased.greatly.with.the.development.of.novel.fabrication.techniques,.which.
provide. robust,. high-throughput. methods. for. the. fabrication. of. topographical. features.
ranging. from. the. submicron. to. the. lowest. resolution. features. obtainable. with. current.
 
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