skip to main content


Search for: All records

Creators/Authors contains: "Chi, Eva"

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Free, publicly-accessible full text available June 1, 2025
  2. Alzheimer's disease (AD) is an uncurable progressive neurodegenerative disease and is the most common cause of dementia. As current understanding of the disease suggests damage begins accumulating a decade before diagnosable symptoms, preventative treatment strategies will require screenings during the asymptomatic state. The high cost of PET and MRI scans make them challenging for the throughput necessary to screen the large population of 65+ individuals most at risk of developing AD. An alternative is near-IR fluorescence imaging, which is less costly and less invasive. We have reported a small-molecule fluorescent sensor able to selectively detect and oxidize the amyloid-β oligomers and fibrils implicated as pathogenic agents in the early development of AD. In this study, we use computational modeling to gain insights into what changes in sensor-protein binding lead to both turn-on fluorescence and turn-on singlet oxygen generation. We utilize molecular dynamics to model sensor behavior in multiple environments, including sensor complexation and protein binding. Both density functional theory (DFT) and time-dependent DFT ab initio calculations are used to monitor intra- and inter-molecular photophysical properties of the molecule. Results show that the structural dynamics of the sensor depends on its binding environment and that the structural changes upon binding are correlated with changes in sensor photophysical characteristics. This investigation contributes to a better understanding of how molecular design gives rise to desirable properties for molecular sensing, leading to improved ability to rationally design near-IR fluorescent sensors for AD. 
    more » « less
  3. Engineering is fundamentally about design, yet many undergraduate programs offer limited opportunities for students to learn to design. This design case reports on a grant-funded effort to revolutionize how chemical engineering is taught. Prior to this effort, our chemical engineering program was like many, offering core courses primarily taught through lectures and problem sets. While some faculty referenced examples, students had few opportunities to construct and apply what they were learning. Spearheaded by a team that included the department chair, a learning scientist, a teaching-intensive faculty member, and faculty heavily engaged with the undergraduate program, we developed and implemented design challenges in core chemical engineering courses. We began by co-designing with students and faculty, initially focusing on the first two chemical engineering courses students take. We then developed templates and strategies that supported other faculty-student teams to expand the approach into more courses. Across seven years of data collection and iterative refinements, we developed a framework that offers guidance as we continue to support new faculty in threading design challenges through core content-focused courses. We share insights from our process that supported us in navigating through challenging questions and concerns.

     
    more » « less
    Free, publicly-accessible full text available February 14, 2025
  4. Abstract

    The aggregation of the intrinsically disordered tau protein into highly ordered β-sheet-rich fibrils is implicated in the pathogenesis of a range of neurodegenerative disorders. The mechanism of tau fibrillogenesis remains unresolved, particularly early events that trigger the misfolding and assembly of the otherwise soluble and stable tau. We investigated the role the lipid membrane plays in modulating the aggregation of three tau variants, the largest isoform hTau40, the truncated construct K18, and a hyperphosphorylation-mimicking mutant hTau40/3Epi. Despite being charged and soluble, the tau proteins were also highly surface active and favorably interacted with anionic lipid monolayers at the air/water interface. Membrane binding of tau also led to the formation of a macroscopic, gelatinous layer at the air/water interface, possibly related to tau phase separation. At the molecular level, tau assembled into oligomers composed of ~ 40 proteins misfolded in a β-sheet conformation at the membrane surface, as detected by in situ synchrotron grazing-incidence X-ray diffraction. Concomitantly, membrane morphology and lipid packing became disrupted. Our findings support a general tau aggregation mechanism wherein tau’s inherent surface activity and favorable interactions with anionic lipids drive tau-membrane association, inducing misfolding and self-assembly of the disordered tau into β-sheet-rich oligomers that subsequently seed fibrillation and deposition into diseased tissues.

     
    more » « less
  5. null (Ed.)
  6. null (Ed.)