Microfluidic Platforms for the Investigation of Intercellular Signalling Mechanisms

Abstract

Intercellular signalling has been identified as a highly complex process, responsible for orchestrating many physiological functions. While conventional methods of investigation have been useful, their limitations are impeding further development. Microfluidics offers an opportunity to overcome some of these limitations. Most notably, microfluidic systems can emulate the in-vivo environments. Further, they enable exceptionally precise control of the microenvironment, allowing complex mechanisms to be selectively isolated and studied in detail. There has thus been a growing adoption of microfluidic platforms for investigation of cell signalling mechanisms. This review provides an overview of the different signalling mechanisms and discusses the methods used to study them, with a focus on the microfluidic devices developed for this purpose.

Investigating intercellular calcium waves by microfluidic gated pinched-flow

“…Further inhibition studies verified that the propagation of cell-to-cell calcium signals depended upon direct cytosolic transfer of molecules via gap junctions. This developed microfluidic method opens a new avenue for intercellular signaling studies (e.g., probing the different existing mechanisms and even how they operate) and drug screening (e.g., screening different potential drugs for more effective agonist or inhibitor) [6,8]. In addition, we anticipate this new method also has other potential applications, such as the study of neurochemistry (e.g., single cell recording) or neuroregeneration [46], the investigation of spatial-temporal dynamics of collective chemosensing [47] and the microfluidic patterning of proteins [48].…”

“…2P B2 1.4(P B2 + P SO ) + P B1 + P SI (8) As shown in Eqs. (7) and (8), W S and D can be adjusted by changing the pressures at B1, SI, B2 and SO.…”

“…Because gap junction mediated cell-to-cell signaling maintains fast equilibration of molecules of low weight, errors in cellular communication can lead to varied deleterious effects such as degenerative and autoimmune diseases [4,5]. However, the mechanisms of intercellular signaling still remain poorly understood due to technical difficulties in realizing localized stimulations in vivo [6][7][8].…”

“…Recently, several reviews have also presented microfluidic chip-based cell-to-cell signaling studies in mammalian systems and modern pharmacology. The authors emphasized that the development of new technologies to identify and quantitatively characterize various communication signals are highly desirable and will surely lead to exciting new advances in this field [6][7][8].…”

Bridging the gap: microfluidic devices for short and long distance cell–cell communication

“…Integrating all these capabilities into one uniform tool is also very difficult. Another challenge is the different mechanisms of cellular communications and the need to have different techniques to study the multiple types of communication pathways, including gap junction signaling, juxtacrine signaling, paracrine signaling, endocrine signaling, and synaptic/direct signaling 12 . There exists no singular platform that can lever all these requirements for studying every pathway in cell-cell communication.…”