Probing cell–cell communication with microfluidic devices

Abstract

Cell-cell communication plays an essential role in organismal development and functionality, and communication errors can lead to deleterious effects such as degenerative and autoimmune diseases. However, the intercellular communication network is extremely complex in multicellular organisms making isolation of the functional unit and study of basic mechanisms technically challenging. Despite the level of complexity and many challenges facing researchers in this area, recent development in microfluidic technology allows miniaturized and integrated devices to perform intercellular communication experiments on-chip. Microfluidics have many advantages, including the ability to accurately mimic the chemical, mechanical, and physical cellular microenvironment, precise spatial and temporal control, dynamic characterization, high throughput, scalability and reproducibility. In this Focus article, we highlight some of the recent works and advances in the application of microfluidics to the study of mammalian intercellular communication with particular emphasis on cell contact and soluble factor mediated communication. In addition, we provide some insights into the likely direction of the future developments in this field.

Three-dimensional manipulation of single cells using surface acoustic waves

“…However, current bioprinting methods are generally hampered by the need to reconstruct and mimic 3D cellto-cell communications and cell-environment interactions. Because of this constraint, bioprinting requires accurate reproduction of multicellular architecture (4,5). Several approaches have been developed to produce complex cell patterns, clusters, assembled arrays, and even tissue structures.…”

Controlling cell–cell interactions using surface acoustic waves

“…Understanding the mechanism and process of cell-cell interaction is critical to many physiological and pathological processes, such as embryogenesis, differentiation, cancer metastasis, immunological interactions, and diabetes (1)(2)(3). Despite significant advances in this field, to further understand how cells interact and communicate with each other, a robust, biocompatible method to precisely control the spatial and temporal association of cells and to create defined cellular assemblies is urgently needed (4). Although several methods have been used to pattern cells, limitations still exist for the demonstrated methods including those that make use of optical, electrical, magnetic, hydrodynamic, and contact printing technologies (5)(6)(7)(8)(9).…”

Microfluidic Platforms for the Investigation of Intercellular Signalling Mechanisms

“…[ 79 ] Notable technologies include super-resolution fl uorescent microscopy techniques, such • Reduces consumption of costly reagents [76] • Allows rapid change of microenvironment (e.g. temperature) [8,9] • Increases the concentration of secreted soluble signals (e.g. RANK-L, MCP-1 and IL-8) [12a] Precise spatial and temporal control over fl ow variables and chemical concentrations…”

“…• Allows studying temporal dynamics of cell signalling mechanisms [32,77] • Facilitates tuning the diffusion to convection ratio to distinguish between autocrine and paracrine signalling mechanisms [39] • Allows precise control over the surface chemistry of the microfl uidic structures [8] • Enables precise control over shear stress induced cell signalling mechanisms [8,23] • Provides scalability in cell signalling analysis [8] • Allows mimicking of in-vivo conditions [8,48] Precise cell patterning • Enables formation of customised cell patterns [5b , 8] • Allows mimicking of in-vivo conditions [8,48] • Allows studying cell signalling down to the single cell level [10] Integration with other components and technologies • Enables customised microdevices capable of sequential processes such as fi ltering, mixing and heating [78] • Allows mimicking of in-vivo conditions [8,48] Parallelisation and automation • Enables multiple assays either under the same or different conditions to be run at the same time [54,55,76] • Enables high throughput experiments [8[ • Eliminates time consuming, labour-intensive processes [76] • Much cheaper than conventional fl uid-handling robots [76] small 2014, DOI: 10.1002/smll.201401444 as stochastic optical reconstruction microscopy (STORM), capable of recording dynamic processes in live cells with nanometer resolution. [ 80 ] Detection at the single-molecule level would be very useful in signalling investigations, although on-chip STORM is still in development.…”

“…[ 5a , d , 7 ] Furthermore, the characteristics of microfl uidics and the benefi ts it bestows make it well suited to intercellular signalling investigations. [ 8 ] Firstly, microfl uidics enables precise and dynamic control over a defi ned microenvironment. This includes spatial and temporal control over stimuli (including chemical, physical, and mechanical stimuli) and cells (singular cells or cell clusters); allowing cell signalling events to be manipulated, characterised dynamically, and quantifi ed.…”