Biomedical Engineering Reference
In-Depth Information
Lateral travelling waves with a characteristic spatial scale have been reported in
various types of cells other than keratocyte. For instance, a spatiotemporal protru-
sion pattern similar to that of the global protruding region and the underlying mech-
anism can be explained in relation to the activation of the GTPases, Rac1, Cdc42
and RhoA (Machacek et al.
2009
; Kunida et al.
2012
). Concerning the spatiotempo-
ral pattern of the APDs in Fig.
6.6b
, similar travelling wave patterns caused by
an unidentifi ed mechanism are shown in mouse T cells and fl y wing disk cells
(Dobereiner et al.
2006
). The multiscale analysis described in this section has fur-
ther clarifi ed that the lateral traveling waves localize not only on one characteristic
spatiotemporal scale, but also exhibits a spatiotemporally nested structure.
6.5
Methodology to Shed Light on Multiscale Property
of Biological Systems
Multiscale is a remarkable property of biological systems. The structure and function
of these systems are realized by mechanisms that integrate intra- (Novak and Tyson
2008
) and inter-scale (Schnell et al.
2007
; Papin et al.
2005
; Noble
2008
; Maus et al.
2011
) interactions across a lot of processes that occur at molecular, cellular, tissue,
and whole-organism levels at various spatiotemporal scales. Key to understand such
multiprocess and multiscale systems is methodologies that cuts across diverse scales
to bring about integrative understanding of downward and upward causation occurring
between different levels in the inter-scale interactions (Dada and Mendes
2011
).
The most appropriate approach (Kitano
2002
; Twycross et al.
2010
) should be
selected based on the biological feature to be investigated, as well as the stage of the
research (Liu and Fletcher
2009
). The fi rst stage involves clarifi cation of the components
in the system, and the system network structure of causation in the inter-scale interactions
among the components as well as downward and upward causation their intra-scale
interactions (Kitano
2002
). Next stage is analysis of the system dynamics. More
advanced stage is development of a system control method. The goal of our understanding
is supposed to identify of strategies to modify and construct the systems.
Indeed, a range of approaches have been developed and successfully used to shed
light on hierarchical mechanisms that underlie biological phenomena, for instance,
an intrinsic self-organizing program in complex tissue morphogenesis (Eiraku et al.
2011
,
2012
), spatially organized signalling through chemical and mechanical
factors for branching morphogenesis in organotypic cultures (Nelson et al.
2006
;
Gjorevski and Nelson
2010
) and cooperative interactions among molecules for
symmetry break in myofi brillogenesis (Grosberg et al.
2011
).
6.6
Conclusion
In this chapter, we discussed a methodology for top-down image-based multiscale
analysis and demonstrated its use using an example. The analysis successfully
highlights the hierarchical properties of organized lamellipodial protrusion driven
