Chapter 12 - Microfluidics for mechanobiology of model organisms
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)
References (209)
- et al.
PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue
Developmental Cell
(2013) - et al.
Microfluidics for the analysis of behavior, nerve regeneration, and neural cell biology in C. elegans
Current Opinion in Neurobiology
(2009) - et al.
Biochemical and structural applications of scanning force microscopy
Current Opinion in Structural Biology
(1994) - et al.
Design and operation of a microfluidic sorter for Drosophila embryos
Sensors and Actuators B: Chemical
(2004) - et al.
Single-cell trapping and impedance measurement utilizing dielectrophoresis in a parallel-plate microfluidic device
Sensors and Actuators B: Chemical
(2014) - et al.
Rare cell isolation and analysis in microfluidics
Lab on a Chip
(2014) - et al.
Small but perfectly formed? Successes, challenges, and opportunities for microfluidics in the chemical and biological sciences
Chem
(2017) Mechanotransduction in C. elegans morphogenesis and tissue function
- et al.
Zebrafish: A model system for the study of human disease
Current Opinion in Genetics & Development
(2000) - et al.
Genetic control of programmed cell death in the nematode C. elegans
Cell
(1986)
Matrix elasticity directs stem cell lineage specification
Cell
Chemotherapy-induced peripheral neuropathy
Role of oxidative stress in Drosophila aging
Mutation Research/DNAging
The zebrafish as a model for complex tissue regeneration
Trends in Genetics
Productive tension: Force-sensing and homeostasis of cell-cell junctions
Trends in Cell Biology
Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence
Biophysical Journal
Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices
Biosensors and Bioelectronics
Studying aging in Drosophila
Methods (San Diego, Calif.)
Forces in tissue morphogenesis and patterning
Cell
Cell tension, matrix mechanics, and cancer development
Cancer Cell
Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis
The FASEB Journal
TipChip: A modular, MEMS-based platform for experimentation and phenotyping of tip-growing cells
Plant Journal
Miniaturized embryo array for automated trapping, immobilization and microperfusion of zebrafish embryos
PLoS ONE
High-Speed AFM and applications to biomolecular systems
Annual Review of Biophysics
Optical trapping, manipulation, and sorting of cells and colloids in microfluidic systems with diode laser bars
Optics Express
On the soul
Great Books of the Western World
Miniaturised nucleic acid analysis
Lab on a Chip
Microfluidics for electrophysiology, imaging, and behavioral analysis of hydra
bioRxiv
Microfluidic laboratories for C. elegans enhance fundamental studies in biology
RSC Advances
Atomic force microscope
Physical Review Letters
The genetics of Caenorhabditis elegans
Genetics
Microbiota-induced changes in Drosophila melanogaster host gene expression and gut morphology
mBio
Tensional homeostasis in dermal fibroblasts: Mechanical responses to mechanical loading in three-dimensional substrates
Journal of Cellular Physiology
Piezo1 links mechanical forces to red blood cell volume
eLife
Expression patterns of cardiac aging in Drosophila
Aging Cell
Bone compressive strength: The influence of density and strain rate
Science
Mechanobiology of skeletal regeneration
Clinical Orthopaedics and Related Research
The neural circuit for touch sensitivity in Caenorhabditis elegans
The Journal of Neuroscience
Green fluorescent protein as a marker for gene expression
Science
Dissection of cardiovascular development and disease pathways in zebrafish
Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors
Nature Neuroscience
On chip cryo-anesthesia of Drosophila larvae for high resolution in vivo imaging applications
Lab on a Chip
Influences of textured substrates on the heart rate of developing zebrafish embryos
Nanotechnology
Ultrasensitive fluorescent proteins for imaging neuronal activity
Nature
On-chip functional neuroimaging with mechanical stimulation in Caenorhabditis elegans larvae for studying development and neural circuits
Lab on a Chip
Automated and controlled mechanical stimulation and functional imaging in vivo in C. elegans
Lab on a Chip
CO2 and compressive immobilization of C. elegans on-chip
Lab on a Chip
Images in cardiovascular medicine: In vivo imaging of the adult Drosophila melanogaster heart with real-time optical coherence tomography
Circulation
Physiological homology between Drosophila melanogaster and vertebrate cardiovascular systems
Disease Models & Mechanisms
Fish and Chips: A microfluidic perfusion platform for monitoring zebrafish development
Lab on a Chip
Cited by (10)
A paradigm shift: Bioengineering meets mechanobiology towards overcoming remyelination failure
2022, BiomaterialsCitation Excerpt :Within simpler organisms, the fruit fly (Drosophila melanogaster), zebrafish (Danio rerio) and frog (Xenopus laevis, Xenopus tropicalis) have attracted the attention of some researchers, mostly due to the relatively high level of conservation of molecular mechanisms between humans and these models [56–59], coupled with the existence of well-established toolboxes for genetic manipulation [60–62]. In addition, these models are very cost-effective, require low-maintenance, have short generation time, are highly compatible with well disseminated microscopy-based techniques and can have the potential to be used in high-throughput (HT) studies [63]. For mechanobiology studies, these organisms are peculiarly interesting due to their optical transparency during the pro-regenerative stages.
Advanced mechanotherapy: Biotensegrity for governing metastatic tumor cell fate via modulating the extracellular matrix
2021, Journal of Controlled ReleaseCitation Excerpt :Recently, animal samples have still deemed as the gold standard. Tough, regulating the tumor microenvironment in mouse samples is intrinsically challenging because of the intricacy, with shortage of devices letting perfect detection of tumorous factors such as the mechanical properties of the ECM [260]. The alternative traditional cell culture methods provide a basic system, which lack the intricacy found in the tumor.
A dual-stimulation strategy in a micro-chip for the investigation of mechanical associative learning behavior of C. elegans
2020, TalantaCitation Excerpt :CS used in the establish of associative learning paradigms is originally neural stimuli, including olfactory [2–4], gustatory [5–7], auditory [8,9], spatial-sensory [10–12], temperature-sensory [13,14], and mechano-sensory stimuli [15,16], etc. Touch-sensation is one of the most fundamental abilities of an organism to cope with mechanical stimuli [17]. Multicellular organisms develop the ability to distinguish whether mechano-stimulus information is useful or harmful based on their past learning experience, allowing them to convert the mechanical stimulus signals into corresponding behavioral changes.
Travelling under pressure - hypoxia and shear stress in the metastatic journey
2023, Clinical and Experimental Metastasis
- 2
Shared first author.