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16 - How to Approach a Coordinated Function: Cell Rigidity-sensing and Force Generation across Length Scales

from Part III - Coordination of complex functions

Published online by Cambridge University Press:  06 August 2018

Michael Sheetz
Affiliation:
Columbia University, New York
Hanry Yu
Affiliation:
National University of Singapore
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Summary

Having discussed specific complex functions in a cell, it is good to understand how a cell integrates them when carrying out a specific process. This will be done in this chapter using fibroblast spreading and adhesion formation as an example. Before this, however, we will recap some of the fundamental concepts discussed in Chapters 1–4. At a whole-cell level, there are many complex functions that we would like to understand in more detail. However, it is difficult to isolate an individual function from the multitude of alternative functions that modify the function of interest. Isolating individual complex functions is made easier by standardizing the in vitro conditions in which cells are growing, so as to cut down on the number of uncontrolled variables. The cells should be synchronized to start from a well-defined state, rather than an array of states. The function of interest must then be followed, from initiation to a later stage, as this can enable the complete sequence of events to be analyzed. At present, this approach has only been used for a handful of complex functions in mammalian cells at the single cell level. By better defining these few functions, however, new paradigms have been provided in which to consider other established functions. Clathrin-dependent endocytosis and cell–matrix adhesion formation are two complex functions where many of the proteins involved are known, and a rough sequence of events has been described in some special circumstances. Those circumstances include specification of the cell environment, cell state, and several other factors that then enable reproducible observations of the cell functions. In the case of cell binding to matrix, there are rapid transitions between distinct cell states. This provides a good example of how cell state changes are needed for complex functions, but they complicate our understanding of the process. In a general context, the descriptions of complex cell functions read like the engineering descriptions of complex functions in factories.

At a practical level, the analysis of functions in single cells requires a number of conditions to be met and we will see in a special case how that can be done. In Chapter 3, complex cellular functions were described as multistep processes that employed many different functional modules. For complex cellular functions to operate under the wide variety of cellular conditions, they need to adapt to the changes in cell behavior that will follow environmental challenges.

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