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. 1997 Nov 11;94(23):12258-62.
doi: 10.1073/pnas.94.23.12258.

Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion

K Francis  1 , B O Palsson
Affiliations

Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion

K Francis et al. Proc Natl Acad Sci U S A. .

Abstract

A cell's ability to effectively communicate with a neighboring cell is essential for tissue function and ultimately for the organism to which it belongs. One important mode of intercellular communication is the release of soluble cyto- and chemokines. Once secreted, these signaling molecules diffuse through the surrounding medium and eventually bind to neighboring cell's receptors whereby the signal is received. This mode of communication is governed both by physicochemical transport processes and cellular secretion rates, which in turn are determined by genetic and biochemical processes. The characteristics of transport processes have been known for some time, and information on the genetic and biochemical determinants of cellular function is rapidly growing. Simultaneous quantitative analysis of the two is required to systematically evaluate the nature and limitations of intercellular signaling. The present study uses a solitary cell model to estimate effective communication distances over which a single cell can meaningfully propagate a soluble signal. The analysis reveals that: (i) this process is governed by a single, key, dimensionless group that is a ratio of biological parameters and physicochemical determinants; (ii) this ratio has a maximal value; (iii) for realistic values of the parameters contained in this dimensionless group, it is estimated that the domain that a single cell can effectively communicate in is approximately 250 micron in size; and (iv) the communication within this domain takes place in 10-30 minutes. These results have fundamental implications for interpretation of organ physiology and for engineering tissue function ex vivo.

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Figures

Figure 1
Figure 1
A schematic illustrating a solitary cell secreting a soluble cyto/chemokine and the concentration gradient that results from the secretion.
Figure 2
Figure 2
The numerical solution to the location-dependent time constant. This time constant is defined as the time it takes to reach half of the ultimate concentration at a particular distance. The dashed line represents τ0.5 = (2.097ζ)2
Figure 3
Figure 3
The propagation distance ζ of soluble cyto/chemokine signal over time. As indicated in the Inset, this distance is defined as the location where c/Km is unity.
Figure 4
Figure 4
Schematic representation of communication distances, illustrating the definition of the effective communication distance ζ0.5 and the maximum communication distance ζ∞. Eq. 12 is plotted for α = 100, using the definition for the location dependent time constant as well as for the steady state solution.
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