Biology subjects

McCarty, N. A.

Publications and source records attributed to McCarty, N. A..

3 recordsLinked to original sources

bioRxiv2026

Membrane-resolved epithelial electrophysiology revealed using extracellular electrochemical impedance spectroscopy (EEIS)

Conventional extracellular epithelial electrophysiology measurements report only bulk transepithelial resistance and capacitance, obscuring the distinct electrical properties of the apical and basolateral membranes. This limitation hinders research of epithelial diseases where dysfunction originates at a specific membrane domain--apical or basolateral--for example in cystic fibrosis or toxin-mediated airway injury. Here we present the extracellular electrochemical impedance spectroscopy (EEIS) technique that extracts membrane-specific electrophysiology by fitting impedance spectra to a two-resistor, two-capacitor (RCRC) model. Using human bronchiolar epithelial monolayers (16HBE), we show a correlation between the electrical time constants of the circuit ({tau}1 = R1 {middle dot} C1,{tau} 2 = R2 {middle dot} C2) and changes in ion permeability of the basolateral and apical membranes. Experimentally, we show that blocking with 5-10 {micro}M GlyH-101 (i.e. decreasing apical membrane permeability), after 10 {micro}M forskolin activation elicits dose dependent{tau} 2 responses that are over 50% larger than{tau} 1and 6-7 minutes faster, whereas 10 {micro}M nystatin (i.e. increasing basolateral membrane permeability) produces{tau} 1 responses 21-25% larger than{tau} 2 and approximately 2 minutes faster. For cystic fibrosis epithelia, we find that elexacaftor/tezacaftor/ivacaftor (ETI) restores the apical membrane electrical response, resulting in a significant 84% higher{tau} 2 than{tau} 1 within the first 10 minutes. It also exhibits a greater than 8 min faster{tau} 2 response relative to{tau} 1 following 10 {micro}M GlyH-101 blocking (i.e., decreasing apical membrane permeability). These results demonstrate that EEIS enables rapid, quantitative, and biologically relevant measurement of apical and basolateral membrane properties in 16HBE epithelia. By providing membrane-specific resolution without the experimental challenges of intracellular electrodes, EEIS establishes a general framework for rapid, membrane-resolved electrophysiology with implications for therapeutic screening.

bioengineering↗

bioRxiv2025

Method for Extracellular Electrochemical Impedance Spectroscopy on Epithelia

Epithelial tissues form barriers to the flow of ions, nutrients, waste products, bacteria, and viruses. The conventional electrophysiology measurement of transepithelial resistance (TER) can quantify epithelial barrier integrity, but does not capture all the electrical behavior of the tissue or provide insight into membrane specific properties. Electrochemical impedance spectroscopy, in addition to measurement of TER, enables measurement of transepithelial capacitance (TEC) and a ratio of electrical time constants for the tissue, which we term membrane ratio. This protocol describes how to perform galvanostatic electrochemical impedance spectroscopy on epithelia using commercially available cell culture inserts and chambers, detailing the apparatus, electrical signal, fitting techniques, and error quantification. The measurement can be performed in approximately one minute using instrumentation capable of galvanostatic sinusoidal signal processing (4 A amplitude, 2 Hz-50 kHz). All fits to the model have less than 10 {Omega} mean absolute error, revealing repeatable values distinct for each cell type. On representative retinal pigment (n=3) and bronchiolar epithelial samples (n=4), we measured TER 500-667 {Omega}.cm2 and 955-1034 {Omega}.cm2, within the expected range, TEC 3.65-4.10 F/cm2 and 1.07-1.10 F/cm2, and membrane ratios 18-22 and 1.9-2.2, respectively.

bioengineering↗

bioRxiv2019

Molecules To Mankind: Bridging Laboratory And Population Training

Aim/PurposeTodays biomedical researchers are expected to apply understanding of basic biology to improve human health. Meeting this goal requires mastery of both laboratory and population sciences, each of which has its own knowledge base, techniques, and training paradigms. BackgroundEmory Universitys "Molecules-to-Mankind" (M2M) doctoral pathway was established in 2009 to be an evolving model of interdisciplinary PhD education. M2M supplements fellows home programs, ensuring they receive training in both population and laboratory sciences. MethodologyThe present paper describes the M2M program in detail. Surveys of faculty and fellows were also carried out, and the results are presented herein. ContributionThe M2M program follows a unique model by which doctoral students receive training in both population and laboratory sciences. The present paper describes this model, such that the information can be disseminated to other educational institutions interested in implementing similar programs. FindingsThis unique model facilitates engagement of stakeholders including the fellows home program, dissertation advisor, and Emorys professional schools. Recruited across biomedical PhD and MD/PhD programs, fellows have diverse research experiences and represent "spokes" bound together by the M2M "hub." This hubs central feature is a weekly seminar class where fellows and faculty members gather for open discussion with interdisciplinary speakers with successful research careers, emphasizing speakers who have tied laboratory and population sciences in their own work. This forum provides an encouraging environment for dialogue on all aspects of biomedical research from the science itself, to the speakers career path, and the logistics of garnering institutional support and building transdisciplinary collaborations. A decade since its inception, M2M has a proven track record of shaping early-stage careers for its 49 alumni to date. Recommendations for PractitionersEngaging trainees outside their home doctoral programs can have positive implications on overall quality of education. Recommendation for ResearchersAs interdisciplinary models grow ever more important in biomedical sciences, it is important to further examine the best teaching methods for training the next generation of scientists. Impact on SocietyInterdisciplinary training at the doctoral level is important to produce future cohorts of engaged and versatile scientific leaders. Future ResearchFuture research should continue to explore novel methods of training graduate students at the doctoral level.

scientific communication and education↗