Engineering Approaches to Study Cellular Decision Making

Abstract

In their native environment, cells are immersed in a complex milieu of biochemical and biophysical cues. These cues may include growth factors, the extracellular matrix, cell-cell contacts, stiffness, and topography, and they are responsible for regulating cellular behaviors such as adhesion, proliferation, migration, apoptosis, and differentiation. The decision-making process used to convert these extracellular inputs into actions is highly complex and sensitive to changes both in the type of individual cue (e.g., growth factor dose/level, timing) and in how these individual cues are combined (e.g., homotypic/heterotypic combinations). In this review, we highlight recent advances in the development of engineering-based approaches to study the cellular decision-making process. Specifically, we discuss the use of biomaterial platforms that enable controlled and tailored delivery of individual and combined cues, as well as the application of computational modeling to analyses of the complex cellular decision-making networks.

Keywords: cell–cell communication; extracellular matrix; growth factors; intracellular signaling; microfluidics.

Figure 1

Overview of cues that are received by cells and the engineering approaches covered in this review that can help decode the effects of these cues on cellular decisions.

Figure 2

Cellular responses to variations in a single cue can vary depending on the cue. However, when the same cues are varied in concert, the resulting behavioral landscape can be complex and not obvious from the results of experiments that examined only individual variations.