During my doctoral studies, I worked on the development of micro-scale platforms for investigations of biological structures, encompassing microfluidic devices and patterned surfaces. My current project at Stanford focuses on studying the role of mechanical forces in adaptive resizing of the Drosophila midgut, using novel microsystems.
Doctor of Philosophy, Chalmers University of Technology (2016)
Current Research and Scholarly Interests
The small intestine has the remarkable ability to adapt its size to the availability of resources. It can grow dramatically in size to increase its digestive capacity when food is abundant and shrink to conserve energy when food is scarce. Stem cells play an important role in at least some of the mechanisms which modulate this reversible remodelling of adult organs.
We aim to understand how the stem cells can sense the different levels of functional demand. To address this question, we will exploit the genetic toolbox of the Drosophila and establish a reductionist model of its midgut. We will also develop new micro-scale devices to delivering forces and chemical stimuli. Using this interdisciplinary approach, we will study the interplay between the physical forces in the intestine and the nutrients in the adaptive resizing of the Drosophila midgut.
Using a Microfluidics Device for Mechanical Stimulation and High Resolution Imaging of C. elegans
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
One central goal of mechanobiology is to understand the reciprocal effect of mechanical stress on proteins and cells. Despite its importance, the influence of mechanical stress on cellular function is still poorly understood. In part, this knowledge gap exists because few tools enable simultaneous deformation of tissue and cells, imaging of cellular activity in live animals, and efficient restriction of motility in otherwise highly mobile model organisms, such as the nematode Caenorhabditis elegans. The small size of C. elegans makes them an excellent match to microfluidics-based research devices, and solutions for immobilization have been presented using microfluidic devices. Although these devices allow for high-resolution imaging, the animal is fully encased in polydimethylsiloxane (PDMS) and glass, limiting physical access for delivery of mechanical force or electrophysiological recordings. Recently, we created a device that integrates pneumatic actuators with a trapping design that is compatible with high-resolution fluorescence microscopy. The actuation channel is separated from the worm-trapping channel by a thin PDMS diaphragm. This diaphragm is deflected into the side of a worm by applying pressure from an external source. The device can target individual mechanosensitive neurons. The activation of these neurons is imaged at high-resolution with genetically-encoded calcium indicators. This article presents the general method using C. elegans strains expressing calcium-sensitive activity indicator (GCaMP6s) in their touch receptor neurons (TRNs). The method, however, is not limited to TRNs nor to calcium sensors as a probe, but can be expanded to other mechanically-sensitive cells or sensors.
View details for DOI 10.3791/56530
View details for Web of Science ID 000426453400028
View details for PubMedID 29553526
Microfluidics for mechanobiology of model organisms.
Methods in cell biology
2018; 146: 217–59
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.
View details for DOI 10.1016/bs.mcb.2018.05.010
View details for PubMedID 30037463
Pneumatic stimulation of C. elegans mechanoreceptor neurons in a microfluidic trap.
Lab on a chip
New tools for applying force to animals, tissues, and cells are critically needed in order to advance the field of mechanobiology, as few existing tools enable simultaneous imaging of tissue and cell deformation as well as cellular activity in live animals. Here, we introduce a novel microfluidic device that enables high-resolution optical imaging of cellular deformations and activity while applying precise mechanical stimuli to the surface of the worm's cuticle with a pneumatic pressure reservoir. To evaluate device performance, we compared analytical and numerical simulations conducted during the design process to empirical measurements made with fabricated devices. Leveraging the well-characterized touch receptor neurons (TRNs) with an optogenetic calcium indicator as a model mechanoreceptor neuron, we established that individual neurons can be stimulated and that the device can effectively deliver steps as well as more complex stimulus patterns. This microfluidic device is therefore a valuable platform for investigating the mechanobiology of living animals and their mechanosensitive neurons.
View details for DOI 10.1039/c6lc01165a
View details for PubMedID 28207921
View details for PubMedCentralID PMC5360562