Francis K, Palsson B O
Department of Bioengineering, 9500 Gilman Drive, University of California at San Diego, La Jolla, CA 92093-0412, USA.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12258-62. doi: 10.1073/pnas.94.23.12258.
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.
细胞与相邻细胞有效通信的能力对于组织功能乃至其所属生物体的功能至关重要。细胞间通信的一种重要方式是可溶性细胞因子和趋化因子的释放。一旦分泌出来，这些信号分子就会在周围介质中扩散，最终与相邻细胞的受体结合，从而接收信号。这种通信方式既受物理化学传输过程的控制，也受细胞分泌速率的影响，而细胞分泌速率又由遗传和生化过程决定。传输过程的特性已经为人所知一段时间了，关于细胞功能的遗传和生化决定因素的信息也在迅速增加。需要对两者进行同步定量分析，以系统地评估细胞间信号传导的性质和局限性。本研究使用单个细胞模型来估计单个细胞能够有效传播可溶性信号的有效通信距离。分析表明：（i）这个过程由一个单一的关键无量纲组控制，该组是生物学参数与物理化学决定因素的比值；（ii）这个比值有一个最大值；（iii）对于这个无量纲组中包含的参数的实际值，估计单个细胞能够有效通信的区域大小约为250微米；（iv）在这个区域内的通信在10 - 30分钟内发生。这些结果对于解释器官生理学和体外工程组织功能具有重要意义。
