Chapter 12 - Microfluidics for mechanobiology of model organisms

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Abstract

Mechanical stimuli play a critical role in organ development, tissue homeostasis, and disease. Understanding how mechanical signals are processed in multicellular model systems is critical for connecting cellular processes to tissue- and organism-level responses. However, progress in the field that studies these phenomena, mechanobiology, has been limited by lack of appropriate experimental techniques for applying repeatable mechanical stimuli to intact organs and model organisms. Microfluidic platforms, a subgroup of microsystems that use liquid flow for manipulation of objects, are a promising tool for studying mechanobiology of small model organisms due to their size scale and ease of customization.

In this work, we describe design considerations involved in developing a microfluidic device for studying mechanobiology. Then, focusing on worms, fruit flies, and zebrafish, we review current microfluidic platforms for mechanobiology of multicellular model organisms and their tissues and highlight research opportunities in this developing field.

Introduction

This chapter discusses the current state and future opportunities in the field of microfluidics for mechanobiological studies of multicellular model organisms. We define the concept of mechanobiology and describe several model organisms and their advantages for mechanobiological studies. We discuss how microfluidic platforms could be used to manipulate and apply repeatable stimuli, examine design considerations for devices, and review prior work on microfluidics for mechanobiology of model organisms and their tissues. We hope this chapter will be helpful for engineers interested in developing tools for model organisms, and for biologists interested in learning how microfluidic technologies can benefit their research goals.

Section snippets

Mechanobiology

Research in medicine and biology has largely focused on the biochemical nature of development, homeostasis, and disease, resulting in transformative insights Broderick et al., 2014, Ellis and Horvitz, 1986, Fire et al., 1998, Kok et al., 2015, Nüsslein-Volhard and Wieschaus, 1980, Walther et al., 2015. However, mechanical signaling also plays crucial roles in these processes Janmey and Miller, 2011, Thompson, 1942, Vining and Mooney, 2017, including tissue patterning in development Bardet et

Multicellular Model Organisms

Model organisms are widely-studied nonhuman systems in biological research, ranging from simple single cells (e.g., Escherichia coli) to animals like mice. Selection of a model organism is dictated by the complexity required to address the research question and the convenience of the experiment. For investigations of responses to mechanical stimuli in the context of differentiated and distinct organs, higher-order multicellular organisms provide an attractive platform. Caenorhabditis elegans

Design Considerations for Microfluidics

The development of microfluidic devices began by taking advantage of fluid motion physics in the laminar flow regime (Whitesides, 2006). Devices capable of complex reactions that involve mixing and multiplexing were designed for chemical synthesis Elvira et al., 2013, Hung et al., 2006, Lignos et al., 2016 and micro total analysis Auroux et al., 2004, Heiland et al., 2017, Jia et al., 2016.

Microfluidic devices for research involving biological cells soon followed (Chiu et al., 2017), because,

Microfluidics for Mechanobiology of Model Organisms

Many of the design considerations discussed above apply to designing new microfluidic devices for mechanobiology as well as to adapting existing devices for studying other model organisms. Prior work can inform future developments in this field, so reviewing existing devices is an important part of the process for designing new ones. To this end, this section focuses on existing microfluidic platforms for mechanobiological studies, as defined above (Fig. 1). Many microfluidic devices have been

Conclusion

Microfluidic technologies are opening doors to mechanobiological studies of multicellular model organisms and their tissues. Worms, fruit flies, and zebrafish are excellent candidates for mechanobiological study in microfluidics because they share fundamental characteristics with more complex organisms, are amenable to genetic techniques, can be cultivated in the lab with relative simplicity, and have the proper size to fit in microfluidics. Further integration of mechanical actuation into

Acknowledgments

We thank Dave Wallace for assistance with graphics and Sandra N. Manosalvas-Kjono, Purim Ladpli, and Farah Memon for helpful discussions. This work was supported in part by the National Institutes of Health under grants R01EB006745, R01GM116000, R01NS047715, R21HL13099301, and F31NS100318, National Science Foundation under grants EFRI MIKS 1136790 and CMMI 166243, Stanford Bio-X IIP, a gift from the G. Harold & Leila Y. Mathers Foundation, and fellowships from the Swedish Research Council (VR)

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