Collaborative Research Centre 1027

Microfluidics developed rapidly in recent years and is nowadays a versatile tool in research labs to fabricate and, maybe more importantly, analyze bio-chemical materials, bearing the potential for increased industrial and medical applications. Some of the difficulties inherent in continuous microfluidics, like the axial dispersion, led to the development of droplet-based microfluidics, which allows to allocate a certain amount of liquid or cells into individual (typically surfactant stabilized) emulsion droplets and handle them with superior control. However, the interesting is not always inside a droplet but might be as well located right at its interface.

We will give a brief overview to microfluidics and its applications starting from continuous microfluidics to droplet based microfluidics and will dwell on a more recent concept called “droplet interface bilayer”. When using e.g. (phospho-) lipids as surfactants to stabilize emulsion droplets, a solvent-free bilayer is formed within seconds after contacting two of those stabilized droplet interphases. This offers the possibility in droplet based microfluidics to produce, study and manipulate unsupported lipid bilayer, which can be considered as artificial cell membranes.

Ciliated surfaces and mucociliary transport plays an important role in human physiology, and biomechanical defects are associated with severe clinical symptoms, including recurrent lung infection and infertility. However, we incompletely understand the rules and processes by which ciliated tissues form and achieve collective transport functions, limiting our ability to model and study disease processes. My research addresses this challenge. I focus on elucidating the biomechanics and (self-)organizing design principles of ciliated tissues using a varity of in vitro, in vivo, and in silico model systems, and I then leverage these insights to investigate mechanisms of human airway disease in Organ Chip models. Specifically, I develop quantitative imaging and modeling tools to explore the following 3 key questions: (1) What are the structure-function relationships that link the mechanics of the individual ciliated cell to the fluid transport functions emergent at the tissue scale?  (2) What are the chemo-mechanical cues and feedback loops that guide ciliated cells to form organized populations with collective behaviors? (3) How do ciliated tissues interact with their physical and biological environment, including bacterial partners, and what are their mechanical failure modes in human airway disease? Here, I will discuss case studies that reveal universal design constraints and parameters of ciliated tissues as well as a new pathogenic mechanism in asthmatic airways. I will also discuss the development of human Airway Chip technology for transferring these insight to biomedical research, including drug testing and development.

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