Biology Reference
In-Depth Information
FIGURE 27.4
Sorting of more adhesive cells (red) to the inside of less adhesive neighbours (blue).
of cells.
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A recent example
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used L cells, a cell line that has very little natural mutual adhe-
sion. L cells were transfected with cadherin 2, different clones expressing the molecule at
different surface densities (just because of the random process of integration of the
cadherin2
transgene). As pure colonies of single clones, the cells aggregated in proportion to the density
of cadherin 2 they expressed. Measurements of surface tension, made by measuring the force
required to crush an aggregate so that its height was half of its width, revealed surface
tension to be in proportion to cadherin density. When labelled clones were mixed, they sorted
out so that the more adhesive clone was surrounded by the less adhesive clone (
Figure 27.4
).
Although this experiment used transfection with just one molecule rather than a complex
morphogenetic mechanism, the basic idea is exactly in line with the idea of synthetic
morphology: to make 'dumb' cells capable of a morphogenetic process by engineering some-
thing into them.
Although little has been done to apply the multi-component synthetic biology to morpho-
genesis, it has already been applied to other (arguably simpler) aspects of developmental
biology such as pattern formation. An example drawn from this area will serve to illustrate
the general approach.
A long-standing model for patterning by a morphogenetic gradient is Lewis Wolpert's
'French Flag' (
Figure 27.5
a),
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in which cells become one of three types ('red', 'white' or
'blue' in the model) according to whether the concentration of a signalling molecule is below
threshold 1, between threshold 1 and threshold 2, or above threshold 2. The hardest cell
behaviour to explain is that of the white stripe, the cells of which detect that the concentration
of the signalling molecule is between two thresholds. One hypothesis about how they might
do this involves a feed-forward circuit like that in
Figure 27.5
b, with its 'arms' having
different efficiencies. To test the feasibility of this hypothetical mechanism in the context of
real cells, Basu and colleagues constructed a version of it in the bacterium
Escherichia coli.
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The signalling molecule was AHL, detected by the LuxR system. In the engineered system,
binding of AHL by the LuxR protein allows the expression of two genes, cI and LacI*, both of
which are repressors of transcription; cI represses the transcription of LacI. Transcription of
the output gene of the system, green fluorescent protein (GFP), is repressed by either LacI,
