Biomedical Engineering Reference
In-Depth Information
Chapter 10
Microchannels
10.1 Biological Introduction
Cell migration on and within matrix environments plays a critical role in a
huge number of physio-pathological phenomena, both during embryo devel-
opment and in the adult organism, as observed in the introduction of the
previous chapter.
In particular, tumor cells are able to abandon their primary site and mi-
grate through the surrounding parenchyma, in order to enter the circulatory
system and invade other healthy tissues. On this journey, cancer individuals
need to continuously regulate their migratory and invasive behavior, as they
are exposed to a variety of biochemical and biomechanical interactions, mod-
ulated both by the biophysics and by the microstructure of the environment
[110, 141, 218]. In vivo connective tissues can, in fact, provide interstitial
extracellular matrices (ECMs) with heterogeneous composition, density, and
organization: they can comprise both loose regions formed by sparse collage-
nous fibers and areas with tightly packed threads.
In the first case, analyzed in Chapter 9 and in several experimental
[122, 124, 146, 409] and theoretical [353, 421, 422] works, important physi-
cal determinants of cell movement include the degree of ECM alignment, the
width of resulting pores, and the ECM stiffness.
In the second case, matrix environments behave instead as physical bar-
riers, adjacent to channel/track-like spaces, which, depending on their di-
mensionality, may either guide, hinder, or completely prevent cell movement
[189, 408]. Remarkably, recent studies have reported that cells achieve signif-
icant movement in highly constrained physical spaces, determined by dense
matrices, by drastic morphological deformations, in addition (or even in sub-
stitution [411]) of the proteolytical degradation of the local environment [408].
The repeated adaptation of cell shape requires substantial reorganization both
of the cytoskeleton and of other organelles, and in particular of the nucleus,
the most voluminous and rigid intracellular compartment. This type of migra-
tion, called amoeboid movement since it is associated with flexible amoeba-like
shape changes, proceeds in a poorly adhesive mode and is mostly independent
from specific molecular and biochemical interactions with the surrounding
189
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