Biology Reference
In-Depth Information
17
Using Self-Assembled Monolayers
to Pattern ECM Proteins and Cells on Substrates
Christopher S. Chen, Emanuele Ostuni,
George M. Whitesides, and Donald E. Ingber
1. Introduction
We present a method that uses microcontact printing of alkanethiols on gold
to generate patterned substrates presenting “islands” of extracellular matrix
(ECM) surrounded by nonadhesive regions such that single cells attach and
spread only on the adhesive regions. We have used this micropatterning tech-
nology to demonstrate that mammalian cells can be switched between growth
and apoptosis programs in the presence of saturating concentrations of growth
factors by either promoting or preventing cell spreading
(1)
. From the perspec-
tive of fundamental cell biology, these results suggested that the local differen-
tials in growth and viability that are critical for the formation of complex tissue
patterns may be generated by local changes in cell-ECM interactions. In the
context of cell culture technologies, such as bioreactors and cellular engineer-
ing applications, the regulation of cell function by cell shape indicates that the
adhesive microenvironment around cells can be carefully optimized by pat-
terning a substrate in addition to using soluble factors
(2)
. Micropatterning
technology will play a central role both in our understanding how ECM and
cell shape regulate cell physiology and in facilitating the development of cellu-
lar biosensor and tissue engineering applications
(3-5)
.
Historically, investigations of cellular responses to various adhesive envi-
ronments were limited by a lack of control over the interfacial properties and
the topology of available substrates. It was particularly difficult to generate
substrates patterned with adjacent adhesive and nonadhesive regions. In the
past decade, the technology to engineer the properties of a surface with
molecular-level control and to pattern these substrates with ligands suitable for
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