I am a mechanical engineering PhD student in Prof Beth Pruitt's Microsystems Laboratory. My research interests deal with mechanics of stem cell-derived cardiomyocytes (iPSC-CMs), or heart muscle cells. In particular, I am interested in the effects of geometry and cell-cell adhesions on cell contractile function, cytoskeletal organization, and protein localization. To study questions in this area, I design and fabricate microscale devices. These devices are often made from polyacrylamide or PDMS and allow us to control single cell geometry and adhesions. They also allow for measurement of a number of parameters such as force generation, calcium cycling, and cytoskeletal structure.
Prior to my graduate studies, I completed my bachelor's degree in biomedical engineering at Case Western Reserve University. During this time I worked in a number of labs at Case Western and other universities during summer internships. I worked on projects including lipid nanobubbles as an ultrasound contrast agent and drug delivery system, an implantable nerve scaffold, and cardiomyocyte maturation in vitro.
After earning my undergraduate degree, I spent a year as a Whitaker Fellow doing research in Ralph Mueller's bone biomechanics group at ETH Zurich. There I worked with graduate students to understand how cells embedded within bones respond to high or low forces. For this project, I also developed initial prototypes for microfluidic devices to measure protein expression in single cells.
Honors & Awards
NSF Graduate Research Fellowship Program, NSF (2013 - 2016)
Stanford Graduate Fellowship, Stanford University (2013 - 2016)
Education & Certifications
MS, Stanford University, Mechanical Engineering (2015)
BS, Case Western Reserve University, Biomedical Engineering (2012)
Controlling cell shape on hydrogels using lift-off protein patterning
2018; 13 (1): e0189901
Polyacrylamide gels functionalized with extracellular matrix proteins are commonly used as cell culture platforms to evaluate the combined effects of extracellular matrix composition, cell geometry and substrate rigidity on cell physiology. For this purpose, protein transfer onto the surface of polyacrylamide hydrogels must result in geometrically well-resolved micropatterns with homogeneous protein distribution. Yet the outcomes of micropatterning methods have not been pairwise evaluated against these criteria. We report a high-fidelity photoresist lift-off patterning method to pattern ECM proteins on polyacrylamide hydrogels with elastic moduli ranging from 5 to 25 kPa. We directly compare the protein transfer efficiency and pattern geometrical accuracy of this protocol to the widely used microcontact printing method. Lift-off patterning achieves higher protein transfer efficiency, increases pattern accuracy, increases pattern yield, and reduces variability of these factors within arrays of patterns as it bypasses the drying and transfer steps of microcontact printing. We demonstrate that lift-off patterned hydrogels successfully control cell size and shape and enable long-term imaging of actin intracellular structure and lamellipodia dynamics when we culture epithelial cells on these substrates.
View details for DOI 10.1371/journal.pone.0189901
View details for PubMedCentralID PMC5752030
For whom the cells pull: Hydrogel and micropost devices for measuring traction forces.
2016; 94: 51-64
While performing several functions, adherent cells deform their surrounding substrate via stable adhesions that connect the intracellular cytoskeleton to the extracellular matrix. The traction forces that deform the substrate are studied in mechanotrasduction because they are affected by the mechanics of the extracellular milieu. We review the development and application of two methods widely used to measure traction forces generated by cells on 2D substrates: (i) traction force microscopy with polyacrylamide hydrogels and (ii) calculation of traction forces with arrays of deformable microposts. Measuring forces with these methods relies on measuring substrate displacements and converting them into forces. We describe approaches to determine force from displacements and elaborate on the necessary experimental conditions for this type of analysis. We emphasize device fabrication, mechanical calibration of substrates and covalent attachment of extracellular matrix proteins to substrates as key features in the design of experiments to measure cell traction forces with polyacrylamide hydrogels or microposts. We also report the challenges and achievements in integrating these methods with platforms for the mechanical stimulation of adherent cells. The approaches described here will enable new studies to understand cell mechanical outputs as a function of mechanical inputs and advance the understanding of mechanotransduction mechanisms.
View details for DOI 10.1016/j.ymeth.2015.08.005
View details for PubMedID 26265073
View details for PubMedCentralID PMC4746112
A Novel Internal Fixator Device for Peripheral Nerve Regeneration
TISSUE ENGINEERING PART C-METHODS
2013; 19 (6): 427-437
Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension--traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration.
View details for DOI 10.1089/ten.tec.2012.0021
View details for Web of Science ID 000317734800003
View details for PubMedID 23102114
Formulation and Characterization of Echogenic Lipid-Pluronic Nanobubbles
2010; 7 (1): 49-59
The advent of microbubble contrast agents has enhanced the capabilities of ultrasound as a medical imaging modality and stimulated innovative strategies for ultrasound-mediated drug and gene delivery. While the utilization of microbubbles as carrier vehicles has shown encouraging results in cancer therapy, their applicability has been limited by a large size which typically confines them to the vasculature. To enhance their multifunctional contrast and delivery capacity, it is critical to reduce bubble size to the nanometer range without reducing echogenicity. In this work, we present a novel strategy for formulation of nanosized, echogenic lipid bubbles by incorporating the surfactant Pluronic, a triblock copolymer of ethylene oxide copropylene oxide coethylene oxide into the formulation. Five Pluronics (L31, L61, L81, L64 and P85) with a range of molecular weights (M(w): 1100 to 4600 Da) were incorporated into the lipid shell either before or after lipid film hydration and before addition of perfluorocarbon gas. Results demonstrate that Pluronic-lipid interactions lead to a significantly reduced bubble size. Among the tested formulations, bubbles made with Pluronic L61 were the smallest with a mean hydrodynamic diameter of 207.9 +/- 74.7 nm compared to the 880.9 +/- 127.6 nm control bubbles. Pluronic L81 also significantly reduced bubble size to 406.8 +/- 21.0 nm. We conclude that Pluronic is effective in lipid bubble size control, and Pluronic M(w), hydrophilic-lipophilic balance (HLB), and Pluronic/lipid ratio are critical determinants of the bubble size. Most importantly, our results have shown that although the bubbles are nanosized, their stability and in vitro and in vivo echogenicity are not compromised. The resulting nanobubbles may be better suited for contrast enhanced tumor imaging and subsequent therapeutic delivery.
View details for DOI 10.1021/mp9001816
View details for Web of Science ID 000274015900007
View details for PubMedID 19957968