Biomedical Engineering Reference
In-Depth Information
6
BioMEMS for Cell Biology
Cells are programmed to be exquisitely sensitive
and responsive to their chang-
ing microenvironment. In a healthy organism as well as in a diseased one, cells respond to
local
variations (sometimes in space, sometimes in time, oten in both) of dozens of biochemical and
biophysical signals that intervene in multiple signaling pathways. As schematically depicted in
Figure 6.1
, biochemical signals can be soluble molecules—nutrients, enzymes, inorganic ions,
and growth factors that are secreted by cells that can be adjacent or, for a large animal, as far
as several meters—or immobilized molecules that are anchored to the membrane of adjacent
cells (e.g., membrane receptors and cadherins) or bound to extracellular scafolds, such as the
extracellular matrix (ECM) or bone. Examples of biophysical signals can be membrane volt-
age, molecular conformation, incident light, temperature, and the rigidity or roughness of the
substrate to which the cells are anchored. All these factors may vary locally and temporally in
smooth gradients or in sharp steps.
his microenvironment is far from static. In fact, living systems are nonequilibrium systems
with large luxes of energy and mass lowing through them. In essence, dynamic microenviron-
ments are what life is about: at the heart of any of life's many deining “macroscale” processes—
reproduction, development, motility, immunological response, sensorial perception, wound
healing, and so on—is a vibrant microenvironment orchestrated by cells. Tragically, this tem-
poral component is necessarily lost in static cell culture systems, in which the cells are bathed
in a homogeneous bath for prolonged periods of time. Hence, microluidics (which allow for
spatiotemporal modulation of the soluble environment) and other techniques that allow for
micron-scale modulation of the substrate characteristics, ofer a precious opportunity to recre-
ate physiological conditions that cannot be attained with traditional cell culture substrates.
In this chapter, we will see how BioMEMS technology can be used to increase the biochemi-
cal and biophysical complexity of cell culture microenvironments—so as to trigger, control, or
inluence cellular processes such as adhesion, migration, growth, secretion, and overall gene
expression in a physiologically relevant, quantitative way that
cannot
be achieved with tradi-
tional cell culture tools. For the same price, BioMEMS devices can also be designed to improve
luid handling (automate routing, reduce consumption and disposal of luids) and increase
experimentation throughput, which may simply facilitate research by lowering costs or enable
new single-cell studies of rare-cell behavior.
6.1 An Enabling Technology: The Hurdles
In Chapter 5, we saw how microluidic devices can be used to overcome some of the luid han-
dling limitations—low throughput, high cost—of traditional cell culture methodology. However,
conventional cell culture techniques are limiting for two additional, even more fundamental,
