Biomedical Engineering Reference
In-Depth Information
most suitable surface functionality was obtained using low exposed diazo-naphtoquinone/
novolak imidazole-doped (a commercially available, positive tone) photoresist. hey found
that the attachment selectivity was determined by the change in surface functional groups
rather than by the hydrophobicity contrast.
In sum, the development of more sophisticated surface chemistry techniques and micro-
luidic delivery methods that deposit biologically relevant ligands without long-term toxicity
concerns has displaced the use of nonbiological materials in cell patterning.
2.6 Micropatterns of Cells on Biomolecular Templates
All the methods described in this section were designed to take advantage of the existence of
natural biorecognition interactions between molecules present in the cell membrane and mol-
ecules present on the adhesive substrate. Note that, given multiple observations, attachment
selectivity is remarkably dependent on the medium's serum content, some of the more advanced
work reviewed in the preceding section already incorporated the notion that cells attach pref-
erentially to ECM proteins. Here, we refer to the interactions that allow cell attachment and
trigger cell spreading as “biological adhesiveness.” he substrate molecules may play a passive
role, such as ECM proteins or speciic peptide sequences recognized by integrins in the cell
membrane, or they may play an active role, such as antibodies recognizing molecules on the cell
membrane. Protein physisorption to the pattern background may be impeded by interposing a
“barrier” between the protein solution and the surface—either a physical barrier (e.g., a stencil)
or a chemical barrier (e.g., a SAM which repels protein physisorption). he physisorption barrier
may or may not be removable, or may be removed by chemical or physical means. Physisorption
onto the background may be circumvented altogether by patterning the proteins in dry condi-
tions. he methods reviewed in the next section encompass most of the combinations of the dif-
ferent imaginable strategies (chemisorption/physisorption, permanent/removable barrier, and
ECM/peptides).
In 1975, Paul Letourneau, then at Stanford University, used Carter's nonbiological shadow-
evaporation method to create palladium islands over polyornithine or collagen coatings—and
observed that the palladium was now repulsive relative to the polyornithine or collagen (
Figure
2.25
). Importantly, this article shited the thinking on cellular micropatterning because it
incorporated the notion that cells could adhere to a micropattern by their speciicity to speciic
biomolecules.
Irradiated laminin
Protected laminin
a
b
c
Day 2
DRG
neuron
Fibroblast
25 µm
40 µm
40 µm
FIGURE 2.25
Shadow-patterning.of.metals.and.laminin.to.pattern.neuronal.growth..(a.and.b,.from.
P..C..Letourneau,.“Cell-to-substratum.adhesion.and.guidance.of.axonal.elongation,”.
Dev. Biol.
.44,.
92-101,.1975..Adapted.with.the.permission.of.Elsevier;.c,.from.J. A..Hammarback,.S..L..Palm,.
L.. T.. Furcht,. and. P.. C.. Letourneau,. “Guidance. of. neurite. outgrowth. by. pathways. of. substratum-
adsorbed.laminin,”.
J. Neurosci. Res.
.13,.213-220,.1985..Figure.contributed.by.Paul.Letourneau.)
