Three-Dimensional Chemical Patterns for Cellular Self-Organization

摘要

In nature, three-dimensional (3D) chemical patterns are generated and sustained with precisely controlled spatial and temporal profiles on a variety of length and time scales. Several studies have outlined the need for the development of in vitro methodologies that replicate the 3D spatiotemporal chemical patterns associated with chemotaxis, cell signaling, angiogenesis, homeostasis, and immune surveillance. There are a number of in vitro microfluidic systems that have been developed to mimic in vivo chemical microenvironments, such as the creation of interleukin-8 gradients to study neutrophil chemotaxis. However, microfluidic systems are inherently planar (2D), and their overall size and dependency on external equipment to enable active flow restricts their applicability. Hence, the development of passive systems that enable the diffusion-based formation of 3D chemical patterns is attractive, since these systems can be readily utilized to generate and sustain patterns within cell culture, homogeneous gels, and other stationary media. Existing microparticles and reservoirs can be utilized to create chemical patterns in 3D environments; however, the predominant spatial release profile is spherically symmetric (Figure 1a).