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4 Publications

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    12/14/20 | Label-free imaging of fibroblast membrane interfaces and protein signatures with vibrational infrared photothermal and phase signals.
    Samolis PD, Langley D, O'Reilly BM, Oo Z, Hilzenrat G, Erramilli S, Sgro AE, McArthur S, Sander MY
    Biomed Opt Express. 12/2020;12(1):303-319. doi: 10.1364/BOE.411888

    Label-free vibrational imaging of biological samples has attracted significant interest due to its integration of structural and chemical information. Vibrational infrared photothermal amplitude and phase signal (VIPPS) imaging provide label-free chemical identification by targeting the characteristic resonances of biological compounds that are present in the mid-infrared fingerprint region (3 µm - 12 µm). High contrast imaging of subcellular features and chemical identification of protein secondary structures in unlabeled and labeled fibroblast cells embedded in a collagen-rich extracellular matrix is demonstrated by combining contrast from absorption signatures (amplitude signals) with sensitive detection of different heat properties (lock-in phase signals). We present that the detectability of nano-sized cell membranes is enhanced to well below the optical diffraction limit since the membranes are found to act as thermal barriers. VIPPS offers a novel combination of chemical imaging and thermal diffusion characterization that paves the way towards label-free imaging of cell models and tissues as well as the study of intracellular heat dynamics.

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    05/12/20 | Intracellular signaling dynamics and their role in coordinating tissue repair.
    Ghilardi SJ, O'Reilly BM, Sgro AE
    Wiley Interdiscip Rev Syst Biol Med. 05/2020;12(3):e1479. doi: 10.1002/wsbm.1479

    Tissue repair is a complex process that requires effective communication and coordination between cells across multiple tissues and organ systems. Two of the initial intracellular signals that encode injury signals and initiate tissue repair responses are calcium and extracellular signal-regulated kinase (ERK). However, calcium and ERK signaling control a variety of cellular behaviors important for injury repair including cellular motility, contractility, and proliferation, as well as the activity of several different transcription factors, making it challenging to relate specific injury signals to their respective repair programs. This knowledge gap ultimately hinders the development of new wound healing therapies that could take advantage of native cellular signaling programs to more effectively repair tissue damage. The objective of this review is to highlight the roles of calcium and ERK signaling dynamics as mechanisms that link specific injury signals to specific cellular repair programs during epithelial and stromal injury repair. We detail how the signaling networks controlling calcium and ERK can now also be dissected using classical signal processing techniques with the advent of new biosensors and optogenetic signal controllers. Finally, we advocate the importance of recognizing calcium and ERK dynamics as key links between injury detection and injury repair programs that both organize and execute a coordinated tissue repair response between cells across different tissues and organs. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Biological Mechanisms > Cell Signaling Laboratory Methods and Technologies > Imaging Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models.

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    04/01/20 | Core Competencies for Undergraduates in Bioengineering and Biomedical Engineering: Findings, Consequences, and Recommendations.
    White JA, Gaver DP, Butera RJ, Choi B, Dunlop MJ, Grande-Allen KJ, Grosberg A, Hitchcock RW, Huang-Saad AY, Kotche M, Kyle AM, Lerner AL, Linehan JH, Linsenmeier RA, Miller MI, Papin JA, Setton L, Sgro A, Smith ML, Zaman M, Lee AP
    Ann Biomed Eng. 04/2020;48(3):905-912. doi: 10.1007/s10439-020-02468-2

    This paper provides a synopsis of discussions related to biomedical engineering core curricula that occurred at the Fourth BME Education Summit held at Case Western Reserve University in Cleveland, Ohio in May 2019. This summit was organized by the Council of Chairs of Bioengineering and Biomedical Engineering, and participants included over 300 faculty members from 100+ accredited undergraduate programs. This discussion focused on six key questions: QI: Is there a core curriculum, and if so, what are its components? QII: How does our purported core curriculum prepare students for careers, particularly in industry? QIII: How does design distinguish BME/BIOE graduates from other engineers? QIV: What is the state of engineering analysis and systems-level modeling in BME/BIOE curricula? QV: What is the role of data science in BME/BIOE undergraduate education? QVI: What core experimental skills are required for BME/BIOE undergrads? s. Indeed, BME/BIOI core curricula exists and has matured to emphasize interdisciplinary topics such as physiology, instrumentation, mechanics, computer programming, and mathematical modeling. Departments demonstrate their own identities by highlighting discipline-specific sub-specialties. In addition to technical competence, Industry partners most highly value our students' capacity for problem solving and communication. As such, BME/BIOE curricula includes open-ended projects that address unmet patient and clinician needs as primary methods to prepare graduates for careers in industry. Culminating senior design experiences distinguish BME/BIOE graduates through their development of client-centered engineering solutions to healthcare problems. Finally, the overall BME/BIOE curriculum is not stagnant-it is clear that data science will become an ever-important element of our students' training and that new methods to enhance student engagement will be of pedagogical importance as we embark on the next decade.

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    03/19/20 | Eco-evolutionary significance of "loners".
    Rossine FW, Martinez-Garcia R, Sgro AE, Gregor T, Tarnita CE
    PLoS Biol. 03/2020;18(3):e3000642. doi: 10.1371/journal.pbio.3000642

    Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stage-arise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies.

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