Cellular Computation and Communication Using Engineered Genetic Regulatory Networks - Cellular Computing - page 132

Figure 7.12 Cell-to-cell communication schematics: (1) The sender cell produces
small signal molecules using certain metabolic pathways. (2) The small molecules
diffuse outside the membrane and into the environment. (3) The signals then diffuse
into neighboring cells and (4) interact with proteins in the receiver cells, thereby
changing signal values.
coordinated behavior. However, in cell aggregates one kind of communication
emerges as especially important—the ability to detect and act on chemical sig-
nal concentration gradients. Such gradient-dependent expression is the building
block of locally unique behavior and cell differentiation, providing one basic
organizing principle for complex patterned development.
We have isolated a specific chemical cell-to-cell signaling mechanism from
a natural biological system, the quorum sensing system of Vibrio fischeri . This
system encodes genes and promoter sequences that allow the controlled ex-
pression of the chemical Vibrio fischeri autoinducer (VAI) within one sender
cell, and the detection and controlled expression of specific genes in another
receiving cell. The free diffusion of the VAI chemical within the medium and
across cell membranes allows the establishment of chemical gradients and the
controlled expression of genetic circuits as a result.
Specifically, we describe the construction and testing of engineered genetic
circuits that exhibit the ability to send a controlled signal from one cell, diffuse
that signal through the intercellular medium, receive that signal within a second
cell, and activate a remote transcriptional response (Figure 7.12). The work re-
ported in this section implements and characterizes cell-to-cell communication
components for the cellular gate library.
Quorum Sensing in Bacteria
Vibrio fischeri is a Gram-negative, bioluminescent, marine prokaryote that nat-
urally occurs in two distinct environments. In seawater, it swims freely at con-
centrations of approximately 10 cells/l. It also grows naturally in a symbiotic