Biomedical Engineering Reference
In-Depth Information
(a)
(b)
(c)
Figure 20.1
(See companion CD for color igure.)
.Cell-substrate.interactions.and.focal.adhesion.formation..(a).Adherent.
cells. form. dynamic. actin-rich. lamellipodia. (arrows). during. the. process. of. cellular. spreading. and. migration.
and.contact.guidance..(b).Cells.probe.the.underlying.topography.with.ine.ilopodial.extensions.(arrows).from.
the.leading.and.trailing.free.edge..(c).Adherent.cells.maintain.cellular.integrity.through.a.dynamic.network.of.
contractile.actin.stress.ibers.(green).that.terminate.in.focal.adhesion.plaques.(red),.molecular.complexes.that.
intimately.connect.the.cytoskeleton.with.the.extracellular.matrix..Scale.bar,.20.μm.
implantation. of. devices.. As. a. growing. number. of. precision. nanofabrication. techniques.
become. available. to. the. cell. biologist,. including. electron. beam. lithography. (Vieu. et. al..
2000;.Gadegaard.et.al..2003),.electrospinning.(Kumbar.et.al..2008;.Orlova.et.al..2011),.poly-
mer.phase.separation.(Muller-Buschbaum.et.al..1998),.and.colloidal.self-assembly.(Arnold.
et. al.. 2004;. Lohmuller. et. al.. 2011),. it. becomes. possible. to. begin. to. dissect. out. the. effects.
of. nanotopography. on. cellular. function. and. to. use. these. nanomaterials. and. devices. as.
noninvasive.tools.to.asses.cellular.processes.
Adherent.cells.are.complex,.self-sustaining.units.(Schwarz.et.al..2006).that.require.extra-
cellular.matrix.(ECM).anchorage.in.order.to.proliferate.and.undergo.differential.function.
(Triplett.and.Pavalko.2006)..Cells.actively.probe.the.physical.properties.of.the.ECM;.their.
contractile.machinery.facilitating.the.formation.of.polarized.“lamellipodia”.(Figure.20.1A).
(Abercrombie.et.al..1970;.Dalby.et.al..2004b;.Zinger.et.al..2004).and.ine.hair-like.protru-
sions. termed. “ilopodia”. (Figure. 20.1B),. structures. which. gather. spatial,. topographical,.
and.chemical.information.from.the.ECM.and/or.material.surface.
Initial. cell. tethering. and. ilopodia. exploration. is. followed. by. lamellipodia. rufling.
(Bershadsky. et. al.. 2006),. membrane. activity,. and. cellular. spreading.. With. time,. endog-
enous.matrix.is.secreted.by.the.cells,.and.matrix.assembly.sites.form.on.the.ventral.plasma.
membrane.(Figure.20.1C)..Once.cell-receptor.ligation.has.occurred.with.an.ECM.protein.
motif,. a. signaling-feedback. pathway. initiates. integrin. receptor. clustering. at. the. plasma.
membrane.and.adhesion.plaque.protein.recruitment.(Lim.et.al..2007).
20.3 Focal Adhesion
One.well-studied.process.of.cell-ECM.adhesion.involves.the.activation.and.recruitment.
of. α-. and. β-chain. transmembrane. proteins. termed. integrins. (Cohen. et. al.. 2004).. These.
receptors.bind.speciically.to.motifs.located.on.ECM.molecules.(e.g.,.the.RGD.tripeptide.
motif.found.in.ibronectin,.vitronectin,.and.laminin.[Garcia.2005]).via.their.globular.head.
domains. and. form. discrete. supramolecular. complexes. that. contain. structural. adaptor.
proteins,.such.as.vinculin,.talin,.and.paxillin.(Burridge.et.al..1988;.Zimerman.et.al..2004;.
